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Antioxidants, Volume 8, Issue 3 (March 2019)

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Cover Story (view full-size image) Pulmonary vascular remodeling in pulmonary hypertension is characterized by increased [...] Read more.
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Open AccessArticle Development and Validation of an Analytical Method for Carnosol, Carnosic Acid and Rosmarinic Acid in Food Matrices and Evaluation of the Antioxidant Activity of Rosemary Extract as a Food Additive
Antioxidants 2019, 8(3), 76; https://doi.org/10.3390/antiox8030076
Received: 11 March 2019 / Revised: 22 March 2019 / Accepted: 23 March 2019 / Published: 26 March 2019
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Abstract
Antioxidants are used to prevent the oxidation of foods. When used for food additive purposes, the dosage should be regulated and the functionality evaluated to ensure stability. In this study, we performed a method validation for the quantitative analysis of rosemary extract residues [...] Read more.
Antioxidants are used to prevent the oxidation of foods. When used for food additive purposes, the dosage should be regulated and the functionality evaluated to ensure stability. In this study, we performed a method validation for the quantitative analysis of rosemary extract residues and evaluated the antioxidant activity of rosemary extract in food matrices. The validated method was able to determine rosemary extract under the optimized high-performance liquid chromatography-photodiode array (HPLC-PDA) conditions. Furthermore, the antioxidant activity was evaluated by peroxide value, acid value, and in terms of the residual antioxidant levels in lard oil. For HPLC-PDA analysis, the limit of detection and quantification of rosemary extracts was ranged from 0.22 to 1.73 μg/mL, 0.66 to 5.23 μg/mL and the recoveries of the rosemary extracts ranged from 70.6 to 114.0%, with relative standard deviations of between 0.2% and 3.8%. In terms of antioxidant activity, carnosic acid performed better than carnosol. Furthermore, by evaluation of the residual antioxidant level using HPLC, we found that carnosic acid is more stable in lard oil than carnosol. These results indicate that rosemary extract can be used as an antioxidant and that the analytical method is suitable for the determination of rosemary extract in various food samples. Full article
(This article belongs to the Special Issue Antioxidant Activity of Polyphenolic Plant Extracts)
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Open AccessArticle In Vitro Antioxidant and Antimicrobial Properties of Flower, Leaf, and Stem Extracts of Korean Mint
Antioxidants 2019, 8(3), 75; https://doi.org/10.3390/antiox8030075
Received: 8 March 2019 / Revised: 15 March 2019 / Accepted: 25 March 2019 / Published: 26 March 2019
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Abstract
Traditionally, Agastache rugosa (Korean mint) has been widely used to treat various infectious diseases. The aims of this study were to: (i) determine the phenylpropanoid content of the plant using high-performance liquid chromatography; (ii) undertake total anthocyanin, flavonoid, and phenolic assays; (iii) and [...] Read more.
Traditionally, Agastache rugosa (Korean mint) has been widely used to treat various infectious diseases. The aims of this study were to: (i) determine the phenylpropanoid content of the plant using high-performance liquid chromatography; (ii) undertake total anthocyanin, flavonoid, and phenolic assays; (iii) and evaluate the antioxidant and antibacterial properties of the methanol extracts from the stem, leaves, and flowers of Korean mint. The total anthocyanin, flavonoid, and phenolic content assays showed that the flowers had higher phenolic levels than the stem and leaves. The reducing power, the 2,2-diphenyl-1-picrylhydrazyl superoxide radical scavenging abilities, and the hydrogen peroxide radical scavenging activities were also evaluated so that the antioxidant activities of the extracts from the different plant parts could be evaluated. The flower extracts revealed higher antioxidant properties than the other parts. The antibacterial properties of the methanol extracts from A. rugosa were analyzed by the disc diffusion method, and the flower extracts had higher antibacterial activities against the six bacterial strains used in the study than the other parts. This study provides information on the synergistic antioxidant and antibacterial properties of phenolics derived from the different parts of Korean mint. Full article
(This article belongs to the Special Issue Phenolic Profiling and Antioxidant Capacity in Plants)
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Open AccessArticle Resveratrol Anti-Obesity Effects: Rapid Inhibition of Adipocyte Glucose Utilization
Antioxidants 2019, 8(3), 74; https://doi.org/10.3390/antiox8030074
Received: 27 February 2019 / Revised: 19 March 2019 / Accepted: 22 March 2019 / Published: 26 March 2019
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Abstract
Studies in animal models of diabetes and obesity have shown that resveratrol mitigates complications of metabolic diseases, beyond those resulting from oxidative stress. Furthermore, results obtained with cultured preadipocytes have also revealed that prolonged resveratrol treatment impairs adipogenesis. Considering the role of adipocytes [...] Read more.
Studies in animal models of diabetes and obesity have shown that resveratrol mitigates complications of metabolic diseases, beyond those resulting from oxidative stress. Furthermore, results obtained with cultured preadipocytes have also revealed that prolonged resveratrol treatment impairs adipogenesis. Considering the role of adipocytes in the hypertrophy of fat stores, and keeping in mind that insulin is the main trigger of excessive energy storage during post-prandial periods, the present study aimed to investigate how short-term effects of resveratrol can limit glucose disposal in a gut-adipose tissue axis. We found that resveratrol exhibits a more potent inhibitory capacity towards α-glucosidase than pancreatic lipase activity. Resveratrol also rapidly blunts glucose transport in mature fat cells by counteracting the effect of insulin and insulin-like lipogenic agents. Within two hours, resveratrol also inhibited the incorporation of glucose into lipids of adipocytes, which was unaffected by membrane cholesterol depletion. Moreover, the comparison between adipocytes with invalidated semicarbazide-sensitive amine oxidase activity and their control, or between resveratrol and several inhibitors, did not indicate that the recently described interaction of resveratrol with amine oxidases was involved in its antilipogenic effect. Caffeine and piceatannol, previously said to interact with glucose carriers, also inhibit lipogenesis in adipocytes, whereas other antioxidant phytochemicals do not reproduce such an antilipogenic effect. This study highlights the diverse first steps by which resveratrol impairs excessive fat accumulation, indicating that this natural molecule and its derivatives deserve further studies to develop their potential anti-obesity properties. Full article
(This article belongs to the Special Issue Natural Products in Health Promotion and Disease Prevention)
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Open AccessArticle Protective Effect of the Hexanic Extract of Eryngium carlinae Inflorescences In Vitro, in Yeast, and in Streptozotocin-Induced Diabetic Male Rats
Antioxidants 2019, 8(3), 73; https://doi.org/10.3390/antiox8030073
Received: 5 March 2019 / Revised: 20 March 2019 / Accepted: 22 March 2019 / Published: 26 March 2019
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Abstract
In the present study, we investigated the composition and antioxidant activity of the hexanic extract of Eryngium carlinae inflorescences by employing in vitro assays to measure antioxidant capacity and 2,2-diphenyl-1-picrylhydrazyl scavenging activity. We also applied the hexanic extract to Saccharomyces cerevisiae, under [...] Read more.
In the present study, we investigated the composition and antioxidant activity of the hexanic extract of Eryngium carlinae inflorescences by employing in vitro assays to measure antioxidant capacity and 2,2-diphenyl-1-picrylhydrazyl scavenging activity. We also applied the hexanic extract to Saccharomyces cerevisiae, under hydrogen peroxide-induced stress. Finally, we tested the extract in male Wistar rats with and without streptozotocin-induced diabetes. The compounds in the hexanic extract were analyzed by gas-chromatography-mass spectrometry, which revealed mainly terpenes and sesquiterpenes, including (Z)β-farnesene (38.79%), β-pinene (17.53%), calamene (13.3%), and α-farnesene (10.38%). In vitro and in S. cerevisiae, the extract possessed antioxidant activity at different concentrations, compared to ascorbic acid (positive control). In normoglycemic and hyperglycemic rats, oral administration of 30 mg/kg of the extract reduced blood glucose levels; lipid peroxidation in liver, kidney and brain; protein carbonylation; and reactive oxygen species (ROS) production. It also increased catalase activity in the brain, kidneys and liver. These findings show that this hexanic extract of E. carlinae inflorescences possessed antioxidant properties. Full article
(This article belongs to the Special Issue Antioxidants in Oxidative Stress Diseases)
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Open AccessReview Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation
Antioxidants 2019, 8(3), 72; https://doi.org/10.3390/antiox8030072
Received: 15 February 2019 / Revised: 19 March 2019 / Accepted: 20 March 2019 / Published: 25 March 2019
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Abstract
Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end [...] Read more.
Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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Open AccessArticle The Strong Antioxidant Sheep/Goat Whey Protein Protects Against mTOR Overactivation in Rats: A Mode of Action Mimicking Fasting
Antioxidants 2019, 8(3), 71; https://doi.org/10.3390/antiox8030071
Received: 18 February 2019 / Revised: 21 March 2019 / Accepted: 21 March 2019 / Published: 23 March 2019
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Abstract
Whey protein, a by-product of the cheese industry, can be putatively used as a functional food due to its beneficial health properties. The main objective of the present study was to assess in vivo the effect of a sheep/goat whey protein on the [...] Read more.
Whey protein, a by-product of the cheese industry, can be putatively used as a functional food due to its beneficial health properties. The main objective of the present study was to assess in vivo the effect of a sheep/goat whey protein on the plasma amino acid profile and mammalian target of rapamycin (mTOR), a regulator of skeletal myogenesis. A control group was fed with a standard commercial diet while the experimental group received a standard commercial diet plus sheep/goat whey protein for 28 days. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted to determine plasma amino acid levels while the expression of p70-S6 Kinase 1 (p70-S6K1) in liver and quadriceps muscles was quantified and used as a biomarker of mTOR activity. The results obtained showed a decrease in the levels of essential and branched-chain amino acids (BCAAs) in the experimental group. Furthermore, p70-S6K1 expression was decreased in the liver of rats consumed whey protein. In conclusion, the reduction of amino acid levels and the concomitant inactivation of mTOR imply that whey could potentially act protectively against disorders induced by mTOR overactivation. Intriguingly, this mode of action mimics fasting, an approach with established advantageous health effects. Full article
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Open AccessArticle Strawberry Intake Ameliorates Oxidative Stress and Decreases GABA Levels Induced by High-Fat Diet in Frontal Cortex of Rats
Antioxidants 2019, 8(3), 70; https://doi.org/10.3390/antiox8030070
Received: 6 February 2019 / Revised: 5 March 2019 / Accepted: 12 March 2019 / Published: 20 March 2019
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Abstract
It has been proposed that there is a correlation between high-fat diet (HFD), oxidative stress and decreased γ-aminobutyric acid (GABA) levels, but this has not been thoroughly demonstrated. In the present study, we determined the effects of strawberry extract intake on the oxidative [...] Read more.
It has been proposed that there is a correlation between high-fat diet (HFD), oxidative stress and decreased γ-aminobutyric acid (GABA) levels, but this has not been thoroughly demonstrated. In the present study, we determined the effects of strawberry extract intake on the oxidative stress and GABA levels in the frontal cortex (FC) of obese rats. We observed that an HFD increased lipid and protein oxidation, and decreased GABA levels. Moreover, UV-irradiated strawberry extract (UViSE) decreased lipid peroxidation but not protein oxidation, whereas non-irradiated strawberry extract (NSE) reduced protein oxidation but not lipid peroxidation. Interestingly, NSE increased GABA concentration, whereas UViSE was not as effective. In conclusion, our results suggest that an HFD increases oxidative damage in the FC, whereas strawberry extract intake may ameliorate the disturbances associated with HFD-induced oxidative damage. Full article
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Open AccessReview Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR)
Antioxidants 2019, 8(3), 69; https://doi.org/10.3390/antiox8030069
Received: 21 January 2019 / Revised: 7 March 2019 / Accepted: 13 March 2019 / Published: 18 March 2019
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Abstract
Membrane-associated estrogen receptors (ER)-α36 and G protein-coupled estrogen receptor (GPER) play important roles in the estrogen’s rapid non-genomic actions including stimulation of cell proliferation. Estrogen via these receptors induces rapid activation of transcription factor nuclear factor-E2-related factor 2 (Nrf2), a master regulator of [...] Read more.
Membrane-associated estrogen receptors (ER)-α36 and G protein-coupled estrogen receptor (GPER) play important roles in the estrogen’s rapid non-genomic actions including stimulation of cell proliferation. Estrogen via these receptors induces rapid activation of transcription factor nuclear factor-E2-related factor 2 (Nrf2), a master regulator of detoxification and antioxidant systems, playing a key role in the metabolic reprogramming to support cell proliferation. This review highlights the possible mechanism underlying rapid Nrf2 activation via membrane-associated estrogen receptors by estrogen and phytoestrogens. Stimulation of ER-α36-GPER signaling complex rapidly induces Src-mediated transactivation of epidermal growth factor receptor (EGFR) leading to a kinase-mediated signaling cascade. We propose a novel hypothesis that ER-α36-GPER signaling initially induces rapid and temporal activation of NADPH oxidase 1 to generate superoxide, which subsequently activates redox-sensitive neutral sphingomyelinase 2 generating the lipid signaling mediator ceramide. Generation of ceramide is required for Ras activation and ceramide-protein kinase C ζ-casein kinase 2 (CK2) signaling. Notably, CK2 enhances chaperone activity of the Cdc37-Hsp90 complex supporting activation of various signaling kinases including Src, Raf and Akt (protein kinase B). Activation of Nrf2 may be induced by cooperation of two signaling pathways, (i) Nrf2 stabilization by direct phosphorylation by CK2 and (ii) EGFR-Ras-PI 3 kinase (PI3K)-Akt axis which inhibits glycogen synthase kinase 3β leading to enhanced nuclear transport and stability of Nrf2. Full article
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Open AccessEditorial Thioredoxin and Glutaredoxin Systems Antioxidants Special Issue
Antioxidants 2019, 8(3), 68; https://doi.org/10.3390/antiox8030068
Received: 14 March 2019 / Accepted: 16 March 2019 / Published: 18 March 2019
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Abstract
The special issue on Thioredoxin and Glutaredoxin systems (http://www [...] Full article
(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)
Open AccessReview Polyphenols as Potential Attenuators of Heat Stress in Poultry Production
Antioxidants 2019, 8(3), 67; https://doi.org/10.3390/antiox8030067
Received: 1 February 2019 / Revised: 26 February 2019 / Accepted: 28 February 2019 / Published: 18 March 2019
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Abstract
Heat stress is a non-specific physiological response of the body when exposed to high ambient temperatures, which can break the balance of body redox and result in oxidative stress that affects growth performance as well as the health of poultry species. Polyphenols have [...] Read more.
Heat stress is a non-specific physiological response of the body when exposed to high ambient temperatures, which can break the balance of body redox and result in oxidative stress that affects growth performance as well as the health of poultry species. Polyphenols have attracted much attention in recent years due to their antioxidant ability and thus, can be an effective attenuator of heat stress. In this paper, the potential mechanisms underlying the inhibitory effect of polyphenols on heat stress in poultry has been reviewed to provide a reference and ideas for future studies related to polyphenols and poultry production. Full article
(This article belongs to the Special Issue Antioxidants in Poultry Nutrition and Reproduction)
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Open AccessArticle Oxidative Imbalance and Kidney Damage in Cafeteria Diet-Induced Rat Model of Metabolic Syndrome: Effect of Bergamot Polyphenolic Fraction
Antioxidants 2019, 8(3), 66; https://doi.org/10.3390/antiox8030066
Received: 12 February 2019 / Revised: 1 March 2019 / Accepted: 12 March 2019 / Published: 16 March 2019
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Abstract
Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect [...] Read more.
Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress. Full article
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Open AccessArticle Effect of Side Chain Functional Groups on the DPPH Radical Scavenging Activity of Bisabolane-Type Phenols
Antioxidants 2019, 8(3), 65; https://doi.org/10.3390/antiox8030065
Received: 31 January 2019 / Revised: 9 March 2019 / Accepted: 11 March 2019 / Published: 16 March 2019
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Abstract
Methods for improving the antioxidant activity of phenolic compounds have been widely investigated; however, most studies have focused on the structure–activity correlations of substituents on the aromatic rings of catechols or flavonoids. We investigated the influence of side chain functional groups on the [...] Read more.
Methods for improving the antioxidant activity of phenolic compounds have been widely investigated; however, most studies have focused on the structure–activity correlations of substituents on the aromatic rings of catechols or flavonoids. We investigated the influence of side chain functional groups on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of xanthorrhizol and curcuphenol analogues. These compounds were synthesised by the side chain functional group conversion of curcumene, followed by direct oxidation of the aromatic ring. We determined the DPPH radical scavenging activity from the half-maximal effective concentration (EC50) obtained from a DPPH assay in methanol. The positional relationships of the side chain with the aromatic ring and phenolic OH group were determined using density functional theory calculations, and the stability of different conformations was compared. Electron transfer-proton transfer was determined to be the dominant mechanism in the DPPH reaction with xanthorrhizol analogues, based on the correlation between the EC50 and ionisation potential. The radical cation was greatly stabilised in the structure where the side chain functional group was close to the aromatic ring. Stabilisation also depended on the phenolic OH group position. In future antioxidant design, aromatic ring substituent conversion and the use of functional groups far from the OH group or ring should be explored. Full article
(This article belongs to the Special Issue The Chemistry of Antioxidant Activity)
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Open AccessArticle Liver Injury Induced by Carbon Tetrachloride in Mice Is Prevented by the Antioxidant Capacity of Anji White Tea Polyphenols
Antioxidants 2019, 8(3), 64; https://doi.org/10.3390/antiox8030064
Received: 5 February 2019 / Revised: 5 March 2019 / Accepted: 12 March 2019 / Published: 14 March 2019
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Abstract
Anji white tea is a unique variety of green tea that is rich in polyphenols. In this study, the effect of Anji white tea polyphenols (AJWTP) on the prevention of carbon tetrachloride (CCl4)-induced liver injury through its antioxidant properties was studied. [...] Read more.
Anji white tea is a unique variety of green tea that is rich in polyphenols. In this study, the effect of Anji white tea polyphenols (AJWTP) on the prevention of carbon tetrachloride (CCl4)-induced liver injury through its antioxidant properties was studied. Biochemical and molecular biology methods were used to analyze the serum and liver tissue of mice. The antioxidant capacity and liver injury preventive effect of AJWTP were determined, and the mechanism was elaborated. The results showed that AJWTP decreased the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) in mice with liver injury, it increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the serum and liver tissue of mice with liver injury, and it also decreased the amount of malondialdehyde (MDA). Further quantitative polymerase chain reaction (qPCR) results showed that AJWTP upregulated the mRNA expression of Cu/Zn-SOD, Mn-SOD, catalase (CAT), and nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor alpha (IκB-α) and downregulated the expression of nuclear factor κ-light-chain-enhancer of activated B-cells (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in the liver tissue of mice with liver injury. Therefore, AJWTP produces sufficient antioxidant action to prevent liver injury, and the effect increases with the increase in AJWTP concentration. The effect of 200 mg/kg AJWTP was similar to that of the same concentration of the drug (silymarin) used for the treatment of liver injury. This indicates excellent potential for the development and utilization of AJWTP because it is an active substance with excellent antioxidant effects and can prevent liver injury. Full article
(This article belongs to the Special Issue Antioxidant and Anti-inflammatory Properties of Plants Extract)
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Open AccessReview Peroxiredoxin6 in Endothelial Signaling
Antioxidants 2019, 8(3), 63; https://doi.org/10.3390/antiox8030063
Received: 25 January 2019 / Revised: 21 February 2019 / Accepted: 5 March 2019 / Published: 13 March 2019
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Abstract
Peroxiredoxins (Prdx) are a ubiquitous family of highly conserved antioxidant enzymes with a cysteine residue that participate in the reduction of peroxides. This family comprises members Prdx1–6, of which Peroxiredoxin 6 (Prdx6) is unique in that it is multifunctional with the ability to [...] Read more.
Peroxiredoxins (Prdx) are a ubiquitous family of highly conserved antioxidant enzymes with a cysteine residue that participate in the reduction of peroxides. This family comprises members Prdx1–6, of which Peroxiredoxin 6 (Prdx6) is unique in that it is multifunctional with the ability to neutralize peroxides (peroxidase activity) and to produce reactive oxygen species (ROS) via its phospholipase (PLA2) activity that drives assembly of NADPH oxidase (NOX2). From the crystal structure, a C47 residue is responsible for peroxidase activity while a catalytic triad (S32, H26, and D140) has been identified as the active site for its PLA2 activity. This paradox of being an antioxidant as well as an oxidant generator implies that Prdx6 is a regulator of cellular redox equilibrium (graphical abstract). It also indicates that a fine-tuned regulation of Prdx6 expression and activity is crucial to cellular homeostasis. This is specifically important in the endothelium, where ROS production and signaling are critical players in inflammation, injury, and repair, that collectively signal the onset of vascular diseases. Here we review the role of Prdx6 as a regulator of redox signaling, specifically in the endothelium and in mediating various pathologies. Full article
(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)
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Open AccessArticle Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells
Antioxidants 2019, 8(3), 62; https://doi.org/10.3390/antiox8030062
Received: 12 December 2018 / Revised: 1 March 2019 / Accepted: 9 March 2019 / Published: 13 March 2019
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Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although [...] Read more.
Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels. Full article
(This article belongs to the Special Issue H2S in Redox Signaling)
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Open AccessReview Water-soluble CoQ10 as A Promising Anti-aging Agent for Neurological Dysfunction in Brain Mitochondria
Antioxidants 2019, 8(3), 61; https://doi.org/10.3390/antiox8030061
Received: 30 January 2019 / Revised: 19 February 2019 / Accepted: 8 March 2019 / Published: 11 March 2019
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Abstract
Mitochondrial function has been closely associated with normal aging and age-related diseases. Age-associated declines in mitochondrial function, such as changes in oxygen consumption rate, cytochrome c oxidase activity of complex IV, and mitochondrial coenzyme Q (CoQ) levels, begin as early as 12 to [...] Read more.
Mitochondrial function has been closely associated with normal aging and age-related diseases. Age-associated declines in mitochondrial function, such as changes in oxygen consumption rate, cytochrome c oxidase activity of complex IV, and mitochondrial coenzyme Q (CoQ) levels, begin as early as 12 to 15 months of age in male mouse brains. Brain mitochondrial dysfunction is accompanied by increased accumulation of phosphorylated α-synuclein in the motor cortex and impairment of motor activities, which are similar characteristics of Parkinson’s disease. However, these age-associated defects are completely rescued by the administration of exogenous CoQ10 to middle-aged mice via its water solubilization by emulsification in drinking water. Further efforts to develop strategies to enhance the biological availability of CoQ10 to successfully ameliorate age-related brain mitochondrial dysfunction or neurodegenerative disorders may provide a promising anti-aging agent. Full article
(This article belongs to the Special Issue CoQ10 in Longevity)
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Open AccessArticle Chemical Properties, Fatty-Acid Composition, and Antioxidant Activity of Goji Berry (Lycium barbarum L. and Lycium chinense Mill.) Fruits
Antioxidants 2019, 8(3), 60; https://doi.org/10.3390/antiox8030060
Received: 7 February 2019 / Revised: 2 March 2019 / Accepted: 5 March 2019 / Published: 10 March 2019
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Abstract
In this study, the content composition and antioxidant activity of goji berry fruits from two species (Lycium barbarum and Lycium chinense) were assessed. The total carbohydrate and phenolic contents were evaluated using attenuated total reflection Fourier-transform infrared (ATR-FT-IR) spectroscopy, while the [...] Read more.
In this study, the content composition and antioxidant activity of goji berry fruits from two species (Lycium barbarum and Lycium chinense) were assessed. The total carbohydrate and phenolic contents were evaluated using attenuated total reflection Fourier-transform infrared (ATR-FT-IR) spectroscopy, while the antioxidant activity of fruits was examined with two in vitro methods, which are based on the scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2’-azino-bis(3-ethyl-benzthiazoline-sulfonic acid) (ABTS•+) free radicals. The fatty-acid profile was determined using gas chromatography coupled with mass spectrometry (GC-MS). The results of this study indicate that the fruits of L. barbarum present higher concentrations in carbohydrates and phenolics than L. chinense Mill. fruits. Furthermore, the antioxidant activity based on the half maximal inhibitory concentration (IC50) measurements of DPPH• and ABTS•+ free-radical scavenging was higher in L. barbarum than L. chinense Mill. Also, the GCMS analysis confirms the high levels of linoleic, palmitic, and oleic acids contained in the fruits of both species. Finally, the results of this study clearly show that the concentration of bioactive and antioxidant molecules is higher in L. barbarum than in L. chinense fruits, which was also confirmed by ATR-FT-IR measurements. Full article
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Open AccessFeature PaperArticle Maternal Supplementation with Antioxidant Vitamins in Sheep Results in Increased Transfer to the Fetus and Improvement of Fetal Antioxidant Status and Development
Antioxidants 2019, 8(3), 59; https://doi.org/10.3390/antiox8030059
Received: 5 February 2019 / Revised: 3 March 2019 / Accepted: 5 March 2019 / Published: 8 March 2019
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Abstract
Twinning and maternal nutritional restriction leads to fetal hypoxia, oxidative stress, and intrauterine growth restriction (IUGR) in near-term sheep pregnancies. Our aim was to determine the effect of oral supplementation of vitamins C and E in pregnant sheep on maternal and umbilical cord [...] Read more.
Twinning and maternal nutritional restriction leads to fetal hypoxia, oxidative stress, and intrauterine growth restriction (IUGR) in near-term sheep pregnancies. Our aim was to determine the effect of oral supplementation of vitamins C and E in pregnant sheep on maternal and umbilical cord blood concentrations of vitamins C and E and the effects on fetal antioxidant status, growth, and placental efficiency. Sixteen single- and sixteen twin-bearing ewes, grazing natural Patagonian prairies, were selected after transrectal ultrasound at day 30 after mating. Half of ewes from each pregnancy rank were supplemented daily with vitamins C and E, administered orally, from 30 to 140 days of gestation, when maternal jugular and fetal venous cord blood samples were obtained during cesarean section. Fetuses were weighed and sexed. Placental weight in each fetus was also obtained. Blood plasma was harvested for measurements of maternal and fetal vitamins concentration and fetal antioxidant capacity. Maternal administration of vitamin C and E was associated with increased fetal cord levels of both vitamins, improved antioxidant status, and enhanced fetal growth in both singleton and twin pregnancies associated with increased placental efficiency. These results highlight the potential of vitamin C and E supplementation to reduce the impact of IUGR in both livestock and humans. Full article
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Open AccessArticle Co-Enzyme Q10 Supplementation Rescues Cumulus Cells Dysfunction in a Maternal Aging Model
Antioxidants 2019, 8(3), 58; https://doi.org/10.3390/antiox8030058
Received: 26 January 2019 / Revised: 17 February 2019 / Accepted: 1 March 2019 / Published: 8 March 2019
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Abstract
Over the past four decades, due to cultural and social changes, women in the developed world have significantly delayed childbirth. This trend is even worse for patients who attend infertility clinics. It is well-known that live birth rates in women older than 35 [...] Read more.
Over the past four decades, due to cultural and social changes, women in the developed world have significantly delayed childbirth. This trend is even worse for patients who attend infertility clinics. It is well-known that live birth rates in women older than 35 are significantly lower than in those younger, both naturally and with assisted reproduction. Fertility decline is, in part, due to an increase in oocyte aneuploidy that leads to a reduced embryo quality, as well as an increased incidence of miscarriages and birth defects. Here we show that aging-associated malfunction is not restricted to the oocyte, as cumulus granulosa cells also display a series of defects linked to mitochondrial activity. In, both, human and mouse model, a decline in cumulus cell function due to increased maternal age is accompanied by a decreased expression of enzymes responsible for Coenzyme Q (CoQ) production, particularly Pdss2 and CoQ6. In an aged mouse model supplementation with Coenzyme Q10—a potent stimulator of mitochondrial function—restored cumulus cell number, stimulated glucose uptake, and increased progesterone production. CoQ10 supplementation might, thus, improve oocyte and cumulus cells quantity and quality, by improving the mitochondrial metabolism in females of advanced maternal age. Full article
(This article belongs to the Special Issue CoQ10 in Longevity)
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Open AccessArticle Gamma-Tocotrienol Protects the Intestine from Radiation Potentially by Accelerating Mesenchymal Immune Cell Recovery
Antioxidants 2019, 8(3), 57; https://doi.org/10.3390/antiox8030057
Received: 31 January 2019 / Revised: 24 February 2019 / Accepted: 28 February 2019 / Published: 6 March 2019
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Abstract
Natural antioxidant gamma-tocotrienol (GT3), a vitamin E family member, provides intestinal radiation protection. We seek to understand whether this protection is mediated via mucosal epithelial stem cells or sub-mucosal mesenchymal immune cells. Vehicle- or GT3-treated male CD2F1 mice were exposed to total body [...] Read more.
Natural antioxidant gamma-tocotrienol (GT3), a vitamin E family member, provides intestinal radiation protection. We seek to understand whether this protection is mediated via mucosal epithelial stem cells or sub-mucosal mesenchymal immune cells. Vehicle- or GT3-treated male CD2F1 mice were exposed to total body irradiation (TBI). Cell death was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Villus height and crypt depth were measured with computer-assisted software in tissue sections. Functional activity was determined with an intestinal permeability assay. Immune cell recovery was measured with immunohistochemistry and Western blot, and the regeneration of intestinal crypts was assessed with ex vivo organoid culture. A single dose of GT3 (200 mg/kg body weight (bwt)) administered 24 h before TBI suppressed cell death, prevented a decrease in villus height, increased crypt depth, attenuated intestinal permeability, and upregulated occludin level in the intestine compared to the vehicle treated group. GT3 accelerated mesenchymal immune cell recovery after irradiation, but it did not promote ex vivo organoid formation and failed to enhance the expression of stem cell markers. Finally, GT3 significantly upregulated protein kinase B or AKT phosphorylation after TBI. Pretreatment with GT3 attenuates TBI-induced structural and functional damage to the intestine, potentially by facilitating intestinal immune cell recovery. Thus, GT3 could be used as an intestinal radioprotector. Full article
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Open AccessReview Regulation of Smooth Muscle Cell Proliferation by NADPH Oxidases in Pulmonary Hypertension
Antioxidants 2019, 8(3), 56; https://doi.org/10.3390/antiox8030056
Received: 30 January 2019 / Revised: 25 February 2019 / Accepted: 1 March 2019 / Published: 5 March 2019
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Abstract
Hyperproliferation of pulmonary arterial smooth muscle cells is a key component of vascular remodeling in the setting of pulmonary hypertension (PH). Numerous studies have explored factors governing the changes in smooth muscle cell phenotype that lead to the increased wall thickness, and have [...] Read more.
Hyperproliferation of pulmonary arterial smooth muscle cells is a key component of vascular remodeling in the setting of pulmonary hypertension (PH). Numerous studies have explored factors governing the changes in smooth muscle cell phenotype that lead to the increased wall thickness, and have identified various potential candidates. A role for reactive oxygen species (ROS) has been well documented in PH. ROS can be generated from a variety of sources, including mitochondria, uncoupled nitric oxide synthase, xanthine oxidase, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In this article, we will review recent data supporting a role for ROS generated from NADPH oxidases in promoting pulmonary arterial smooth muscle cell proliferation during PH. Full article
(This article belongs to the Special Issue NADPH Oxidase–Mediated ROS in Pulmonary Arterial Hypertension)
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Open AccessArticle Evaluation of the AGE/sRAGE Axis in Patients with Multiple Myeloma
Antioxidants 2019, 8(3), 55; https://doi.org/10.3390/antiox8030055
Received: 23 January 2019 / Revised: 26 February 2019 / Accepted: 3 March 2019 / Published: 4 March 2019
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Abstract
Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM [...] Read more.
Glycative stress influences tumor progression. The aim of the present study was to evaluate the advanced glycation end products/soluble receptor of advanced glycation end products (AGE/sRAGE) axis in patients with multiple myeloma (MM). Blood samples were taken from 19 patients affected by MM and from 16 sex-matched and age-matched healthy subjects. AGE and sRAGE axis were dosed in patients with MM and matched with controls. AGEs were measured by spectrofluorimetric methods. Blood samples for the determination of sRAGE were analyzed by ELISA. AGE levels were significantly reduced in patients with respect to controls. Instead, sRAGE was significantly elevated in patients affected by MM compared to healthy subjects. Moreover, we showed that there was a statistically significant difference in sRAGE according to the heavy and light chain. IgA lambda had significantly higher sRAGE values than IgA kappa, IgG kappa, and IgG Lambda MM patients. From our data emerges the role of the sRAGE/AGE axis in MM. Since AGE is a positive regulator of the activity of RAGE, circulating sRAGE concentrations may reflect RAGE expression and may be raised in parallel with serum AGE concentrations as a counter-system against AGE-caused tissue damage. Serum concentrations of AGE and sRAGE could therefore become potential therapeutic targets. Full article
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Open AccessArticle Proteomic Analyses of Thioredoxins f and m Arabidopsis thaliana Mutants Indicate Specific Functions for These Proteins in Plants
Antioxidants 2019, 8(3), 54; https://doi.org/10.3390/antiox8030054
Received: 11 January 2019 / Revised: 22 February 2019 / Accepted: 25 February 2019 / Published: 2 March 2019
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Abstract
A large number of plastidial thioredoxins (TRX) are present in chloroplast and the specificity versus the redundancy of their functions is currently under discussion. Several results have highlighted the fact that each TRX has a specific target protein and thus a specific function. [...] Read more.
A large number of plastidial thioredoxins (TRX) are present in chloroplast and the specificity versus the redundancy of their functions is currently under discussion. Several results have highlighted the fact that each TRX has a specific target protein and thus a specific function. In this study we have found that in vitro activation of the fructose-1,6-bisphosphatase (FBPase) enzyme is more efficient when f1 and f2 type thioredoxins (TRXs) are used, whilst the m3 type TRX did not have any effect. In addition, we have carried out a two-dimensional electrophoresis-gel to obtain the protein profiling analyses of the trxf1, f2, m1, m2, m3 and m4 Arabidopsis mutants. The results revealed quantitative alteration of 86 proteins and demonstrated that the lack of both the f and m type thioredoxins have diverse effects on the proteome. Interestingly, 68% of the differentially expressed proteins in trxf1 and trxf2 mutants were downregulated, whilst 75% were upregulated in trxm1, trxm2, trxm3 and trxm4 lines. The lack of TRX f1 provoked a higher number of down regulated proteins. The contrary occurred when TRX m4 was absent. Most of the differentially expressed proteins fell into the categories of metabolic processes, the Calvin–Benson cycle, photosynthesis, response to stress, hormone signalling and protein turnover. Photosynthesis, the Calvin–Benson cycle and carbon metabolism are the most affected processes. Notably, a significant set of proteins related to the answer to stress situations and hormone signalling were affected. Despite some studies being necessary to find specific target proteins, these results show signs that are suggest that the f and m type plastidial TRXs most likely have some additional specific functions. Full article
(This article belongs to the Special Issue Thioredoxin and Glutaredoxin Systems)
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Open AccessReview Progesterone, Lipoic Acid, and Sulforaphane as Promising Antioxidants for Retinal Diseases: A Review
Antioxidants 2019, 8(3), 53; https://doi.org/10.3390/antiox8030053
Received: 1 February 2019 / Revised: 21 February 2019 / Accepted: 28 February 2019 / Published: 2 March 2019
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Abstract
Oxidative stress has been documented to be a key factor in the cause and progression of different retinal diseases. Oxidative cellular unbalance triggers a sequence of reactions which prompt cell degeneration and retinal dysfunction, both hallmarks of several retinal pathologies. There is no [...] Read more.
Oxidative stress has been documented to be a key factor in the cause and progression of different retinal diseases. Oxidative cellular unbalance triggers a sequence of reactions which prompt cell degeneration and retinal dysfunction, both hallmarks of several retinal pathologies. There is no effective treatment, yet, for many retinal diseases. Antioxidant treatment have been pointed out to be an encouraging palliative treatment; the beneficial effects documented involve slowing the progression of the disease, a reduction of cell degeneration, and improvement of retinal functions. There is a vast information corpus on antioxidant candidates. In this review, we expose three of the main antioxidant treatments, selected for their promising results that has been reported to date. Recently, the sulforaphane, an isothiocyanate molecule, has been unveiled as a neuroprotective candidate, by its antioxidant properties. Progesterone, a neurosteroid has been proposed to be a solid and effective neuroprotective agent. Finally, the lipoic acid, an organosulfur compound, is a well-recognized antioxidant. All of them, have been tested and studied on different retinal disease models. In this review, we summarized the published results of these works, to offer a general view of the current antioxidant treatment advances, including the main effects and mechanisms described. Full article
(This article belongs to the Special Issue Antioxidants and Retinal Disease)
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Open AccessArticle Non-Mammalian Prdx6 Enzymes (Proteins with 1-Cys Prdx Mechanism) Display PLA2 Activity Similar to the Human Orthologue
Antioxidants 2019, 8(3), 52; https://doi.org/10.3390/antiox8030052
Received: 11 January 2019 / Revised: 20 February 2019 / Accepted: 22 February 2019 / Published: 1 March 2019
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Abstract
Mammalian peroxiredoxin class 6 (Prdx6) are bifunctional enzymes. Non-mammalian Prdx6 enzymes display Cys-based peroxidase activity, but to date their putative phospholipase A2 (PLA2 activities) has not been experimentally investigated. Initially, we observed that five non-mammalian Prdx6 enzymes (enzymes from Arabidopsis thaliana [...] Read more.
Mammalian peroxiredoxin class 6 (Prdx6) are bifunctional enzymes. Non-mammalian Prdx6 enzymes display Cys-based peroxidase activity, but to date their putative phospholipase A2 (PLA2 activities) has not been experimentally investigated. Initially, we observed that five non-mammalian Prdx6 enzymes (enzymes from Arabidopsis thaliana (AtPER1), Triticum aestivum (TaPER1), Pseudomonas aeruginosa (PaLsfA) and Aspergillus fumigatus (AfPrx1 and AfPrxC)) present features compatible with PLA2 activities in mammalian Prdx6 by amino acid sequences alignment and tertiary structure modeling. Employing unilamellar liposomes with tracer amounts of [3H]-1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and thin layer chromatography, all the tested non-mammalian Prdx6 enzymes displayed PLA2 activities, with values ranging from 3.4 to 6.1 nmol/min/mg protein. It was previously shown that Thr177 phosphorylation of human Prdx6 increases its PLA2 activity, especially at neutral pH. Therefore, we investigated if human Erk2 kinase could also phosphorylate homologous Thr residues in non-mammalian Prdx6 proteins. We observed phosphorylation of the conserved Thr in three out of the five non-mammalian Prdx enzymes by mass spectrometry. In the case of the mitochondrial Prdx6 from A. fumigatus (AfPrxC), we also observed phosphorylation by western blot, and as a consequence, the PLA2 activity was increased in acidic and neutral conditions by the human Erk2 kinase treatment. The possible physiological meanings of these PLA2 activities described open new fields for future research. Full article
(This article belongs to the Special Issue Peroxiredoxin 6 as a Unique Member of the Peroxiredoxin Family)
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