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Keywords = metabolic rerouting

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14 pages, 2600 KiB  
Article
MYB Transcriptional Factors Affects Upstream and Downstream MEP Pathway and Triterpenoid Biosynthesis in Chlamydomonas reinhardtii
by Muhammad Anwar, Jingkai Wang, Jiancheng Li, Muhammad Mohsin Altaf and Zhangli Hu
Processes 2024, 12(3), 487; https://doi.org/10.3390/pr12030487 - 28 Feb 2024
Cited by 4 | Viewed by 2634
Abstract
Terpenoids are enormous and different types of naturally occurring metabolites playing an important role in industrial applications. Cost-effective and sustainable production of terpenoids at commercial scale is the big challenge because of its low abundance from their natural sources. Metabolic and genetic engineering [...] Read more.
Terpenoids are enormous and different types of naturally occurring metabolites playing an important role in industrial applications. Cost-effective and sustainable production of terpenoids at commercial scale is the big challenge because of its low abundance from their natural sources. Metabolic and genetic engineering in microorganisms provide the ideal platform for heterologous overexpression protein systems. The photosynthetic green alga Chlamydomonas reinhardtii is considered as a model host for the production of economic and sustainable terpenoids, but the regulation mechanism of their metabolisms is still unclear. In this study, we have investigated the genetic and metabolic synthetic engineering strategy of MYB transcriptional factors (MYB TFs) in terpenoids’ synthesis from C. reinhardtii for the first time. We heterologous overexpressed MYB TFs, specifically SmMYB36 from Salvia miltiorrhiza in C. reinhardtii. MYB upregulated the key genes involved in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Expression of the SQS gene, which is involved in the downstream triterpenoid synthesis pathway, highly accumulated in MYB-overexpression lines of C. reinhardtii. The contents of squalene increased about 90.20 μg/g in MYB-overexpressed lines. Our results propose the rerouting of the carbon flux toward the biosynthesis of triterpenoids upon overexpression of MYB TFs in C. reinhardtii. Our study suggests imperative novel understandings into the regulation mechanisms of C. reinhardtii triterpenoid metabolism through MYB TFs in photosynthetic green microalgae C. reinhardtii. The role of MYB TFs is investigated for the first time in C. reinhardtii, and provides a prodigious potential for recognizing important transcriptional regulators of the MEP pathway as goals for prospective metabolic and genetic manipulation investigation for increased production of triterpenoids. Full article
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33 pages, 4686 KiB  
Article
Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors
by Ilinca Suciu, Johannes Delp, Simon Gutbier, Julian Suess, Lars Henschke, Ivana Celardo, Thomas U. Mayer, Ivano Amelio and Marcel Leist
Antioxidants 2024, 13(1), 49; https://doi.org/10.3390/antiox13010049 - 28 Dec 2023
Cited by 7 | Viewed by 2633
Abstract
To characterize the hits from a phenotypic neurotoxicity screen, we obtained transcriptomics data for valinomycin, diethylstilbestrol, colchicine, rotenone, 1-methyl-4-phenylpyridinium (MPP), carbaryl and berberine (Ber). For all compounds, the concentration triggering neurite degeneration correlated with the onset of gene expression changes. The mechanistically diverse [...] Read more.
To characterize the hits from a phenotypic neurotoxicity screen, we obtained transcriptomics data for valinomycin, diethylstilbestrol, colchicine, rotenone, 1-methyl-4-phenylpyridinium (MPP), carbaryl and berberine (Ber). For all compounds, the concentration triggering neurite degeneration correlated with the onset of gene expression changes. The mechanistically diverse toxicants caused similar patterns of gene regulation: the responses were dominated by cell de-differentiation and a triggering of canonical stress response pathways driven by ATF4 and NRF2. To obtain more detailed and specific information on the modes-of-action, the effects on energy metabolism (respiration and glycolysis) were measured. Ber, rotenone and MPP inhibited the mitochondrial respiratory chain and they shared complex I as the target. This group of toxicants was further evaluated by metabolomics under experimental conditions that did not deplete ATP. Ber (204 changed metabolites) showed similar effects as MPP and rotenone. The overall metabolic situation was characterized by oxidative stress, an over-abundance of NADH (>1000% increase) and a re-routing of metabolism in order to dispose of the nitrogen resulting from increased amino acid turnover. This unique overall pattern led to the accumulation of metabolites known as biomarkers of neurodegeneration (saccharopine, aminoadipate and branched-chain ketoacids). These findings suggest that neurotoxicity of mitochondrial inhibitors may result from an ensemble of metabolic changes rather than from a simple ATP depletion. The combi-omics approach used here provided richer and more specific MoA data than the more common transcriptomics analysis alone. As Ber, a human drug and food supplement, mimicked closely the mode-of-action of known neurotoxicants, its potential hazard requires further investigation. Full article
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21 pages, 6799 KiB  
Article
Deterioration in the Quality of Recalcitrant Quercus robur Seeds during Six Months of Storage at Subzero Temperatures: Ineffective Activation of Prosurvival Mechanisms and Evidence of Freezing Stress from an Untargeted Metabolomic Study
by Agnieszka Szuba, Ewa Marzena Kalemba, Mikołaj Krzysztof Wawrzyniak, Jan Suszka and Paweł Chmielarz
Metabolites 2022, 12(8), 756; https://doi.org/10.3390/metabo12080756 - 17 Aug 2022
Cited by 9 | Viewed by 2719
Abstract
Pedunculate oak (Quercus robur L.) is an economically important forest-forming species in Poland that produces seeds that are sensitive to desiccation; therefore, short-lived seeds are classified as recalcitrant. Such seeds display active metabolism throughout storage. Acorns stored under controlled conditions (moisture content [...] Read more.
Pedunculate oak (Quercus robur L.) is an economically important forest-forming species in Poland that produces seeds that are sensitive to desiccation; therefore, short-lived seeds are classified as recalcitrant. Such seeds display active metabolism throughout storage. Acorns stored under controlled conditions (moisture content of 40%, temperature −3 °C) maintain viability for up to 1.5–2 years. Meanwhile, oaks only produce large numbers of seeds every few years during so-called mast years. This results in a scarcity of good-quality seeds for continuous nursery production and restoration. The recalcitrant storage behavior and the requirements of foresters make it necessary to develop a new protocol for longer acorn storage at lower temperatures. Two storage temperatures were tested: −3 °C (currently used in forest practice) and −7 °C. Our results showed that acorns stored for six months exhibited deterioration and reduced germination capacity, as well as reduced seedling performance, particularly when acorns were stored at −7 °C. To elucidate the decrease in quality during storage, an untargeted metabolomics study was performed for the first time and supported with the analysis of carbohydrates and percentages of carbon (C) and nitrogen (N). Embryonic axes were characterized by a lower C:N ratio and higher hydration. A total of 1985 metabolites were detected, and 303 were successfully identified and quantified, revealing 44 known metabolites that displayed significantly up- or downregulated abundance. We demonstrated for the first time that the significant deterioration of seed germination potential, particularly in seeds stored at −7 °C, was accompanied by an increased abundance of phenolic compounds and carbohydrates but also amino acids and phosphorylated monosaccharides, particularly in the embryonic axes. The increased abundance of defense-related metabolites (1,2,4-Benzenetriol; BTO), products of ascorbic acid degradation (threonic and isothreonic acid), as well as antifreezing compounds (sugar alcohols, predominantly threitol), was reported in seed stored at −7 °C. We hypothesize that seed deterioration was caused by freezing stress experienced during six months of storage at −7 °C, a decline in antioxidative potential and the unsuccessful rerouting of the energy-production pathways. Additionally, our data are a good example of the application of high-throughput metabolomic tools in forest management. Full article
(This article belongs to the Section Plant Metabolism)
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18 pages, 2253 KiB  
Article
Identification of Metabolomic Biomarkers of Long-Term Stress Using NMR Spectroscopy in a Diving Duck
by Asha Perera, Catherine Soos and Karen Machin
Metabolites 2022, 12(4), 353; https://doi.org/10.3390/metabo12040353 - 15 Apr 2022
Cited by 1 | Viewed by 2431
Abstract
Human-induced environmental changes that act as long-term stressors pose significant impacts on wildlife health. Energy required for maintenance or other functions may be re-routed towards coping with stressors, ultimately resulting in fluctuations in metabolite levels associated with energy metabolism. While metabolomics approaches are [...] Read more.
Human-induced environmental changes that act as long-term stressors pose significant impacts on wildlife health. Energy required for maintenance or other functions may be re-routed towards coping with stressors, ultimately resulting in fluctuations in metabolite levels associated with energy metabolism. While metabolomics approaches are used increasingly to study environmental stressors, its use in studying stress in birds is in its infancy. We implanted captive lesser scaup (Aythya affinis) with either a biodegradable corticosterone (CORT) pellet to mimic the effects of a prolonged stressor or a placebo pellet. 1D 1H nuclear magnetic resonance (NMR) spectroscopy was performed on serum samples collected over 20 days after implant surgery. We hypothesized that CORT pellet-induced physiological stress would alter energy metabolism and result in distinct metabolite profiles in ducks compared with placebo (control). Quantitative targeted metabolite analysis revealed that metabolites related to energy metabolism: glucose, formate, lactate, glutamine, 3-hydroxybutyrate, ethanolamine, indole-3- acetate, and threonine differentiated ducks with higher circulatory CORT from controls on day 2. These metabolites function as substrates or intermediates in metabolic pathways related to energy production affected by elevated serum CORT. The use of metabolomics shows promise as a novel tool to identify and characterize physiological responses to stressors in wild birds. Full article
(This article belongs to the Special Issue Metabolites Focused on Wildlife and Conservation Biology)
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18 pages, 2428 KiB  
Article
Reduction in Phosphoribulokinase Amount and Re-Routing Metabolism in Chlamydomonas reinhardtii CP12 Mutants
by Cassy Gérard, Régine Lebrun, Erwan Lemesle, Luisana Avilan, Kwang Suk Chang, EonSeon Jin, Frédéric Carrière, Brigitte Gontero and Hélène Launay
Int. J. Mol. Sci. 2022, 23(5), 2710; https://doi.org/10.3390/ijms23052710 - 28 Feb 2022
Cited by 10 | Viewed by 3290
Abstract
The chloroplast protein CP12 is involved in the dark/light regulation of the Calvin–Benson–Bassham cycle, in particular, in the dark inhibition of two enzymes: glyceraldehyde−3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK), but other functions related to stress have been proposed. We knocked out the unique [...] Read more.
The chloroplast protein CP12 is involved in the dark/light regulation of the Calvin–Benson–Bassham cycle, in particular, in the dark inhibition of two enzymes: glyceraldehyde−3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK), but other functions related to stress have been proposed. We knocked out the unique CP12 gene to prevent its expression in Chlamydomonas reinhardtii (ΔCP12). The growth rates of both wild-type and ΔCP12 cells were nearly identical, as was the GAPDH protein abundance and activity in both cell lines. On the contrary, the abundance of PRK and its specific activity were significantly reduced in ΔCP12, as revealed by relative quantitative proteomics. Isolated PRK lost irreversibly its activity over-time in vitro, which was prevented in the presence of recombinant CP12 in a redox-independent manner. We have identified amino acid residues in the CP12 protein that are required for this new function preserving PRK activity. Numerous proteins involved in redox homeostasis and stress responses were more abundant and the expressions of various metabolic pathways were also increased or decreased in the absence of CP12. These results highlight CP12 as a moonlighting protein with additional functions beyond its well-known regulatory role in carbon metabolism. Full article
(This article belongs to the Special Issue Chloroplast 3.0)
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18 pages, 3646 KiB  
Article
Uncovering the Metabolic and Stress Responses of Human Embryonic Stem Cells to FTH1 Gene Silencing
by Luana Scaramuzzino, Valeria Lucchino, Stefania Scalise, Michela Lo Conte, Clara Zannino, Alessandro Sacco, Flavia Biamonte, Elvira Immacolata Parrotta, Francesco Saverio Costanzo and Giovanni Cuda
Cells 2021, 10(9), 2431; https://doi.org/10.3390/cells10092431 - 15 Sep 2021
Cited by 17 | Viewed by 4943
Abstract
Embryonic stem cells (ESCs) are pluripotent cells with indefinite self-renewal ability and differentiation properties. To function properly and maintain genomic stability, ESCs need to be endowed with an efficient repair system as well as effective redox homeostasis. In this study, we investigated different [...] Read more.
Embryonic stem cells (ESCs) are pluripotent cells with indefinite self-renewal ability and differentiation properties. To function properly and maintain genomic stability, ESCs need to be endowed with an efficient repair system as well as effective redox homeostasis. In this study, we investigated different aspects involved in ESCs’ response to iron accumulation following stable knockdown of the ferritin heavy chain (FTH1) gene, which encodes for a major iron storage protein with ferroxidase activity. Experimental findings highlight unexpected and, to a certain extent, paradoxical results. If on one hand FTH1 silencing does not correlate with increased ROS production nor with changes in the redox status, strengthening the concept that hESCs are extremely resistant and, to a certain extent, even refractory to intracellular iron imbalance, on the other, the differentiation potential of hESCs seems to be affected and apoptosis is observed. Interestingly, we found that FTH1 silencing is accompanied by a significant activation of the nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway and pentose phosphate pathway (PPP), which crosstalk in driving hESCs antioxidant cascade events. These findings shed new light on how hESCs perform under oxidative stress, dissecting the molecular mechanisms through which Nrf2, in combination with PPP, counteracts oxidative injury triggered by FTH1 knockdown. Full article
(This article belongs to the Collection Researches on Normal and Cancer Stem Cells)
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20 pages, 3081 KiB  
Article
Danon Disease-Associated LAMP-2 Deficiency Drives Metabolic Signature Indicative of Mitochondrial Aging and Fibrosis in Cardiac Tissue and hiPSC-Derived Cardiomyocytes
by Giorgia Del Favero, Alois Bonifacio, Teisha J. Rowland, Shanshan Gao, Kunhua Song, Valter Sergo, Eric D. Adler, Luisa Mestroni, Orfeo Sbaizero and Matthew R. G. Taylor
J. Clin. Med. 2020, 9(8), 2457; https://doi.org/10.3390/jcm9082457 - 31 Jul 2020
Cited by 14 | Viewed by 5650
Abstract
Danon disease is a severe X-linked disorder caused by deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Clinical manifestations are phenotypically diverse and consist of hypertrophic and dilated cardiomyopathies, skeletal myopathy, retinopathy, and intellectual dysfunction. Here, we investigated the metabolic landscape of Danon disease [...] Read more.
Danon disease is a severe X-linked disorder caused by deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Clinical manifestations are phenotypically diverse and consist of hypertrophic and dilated cardiomyopathies, skeletal myopathy, retinopathy, and intellectual dysfunction. Here, we investigated the metabolic landscape of Danon disease by applying a multi-omics approach and combined structural and functional readouts provided by Raman and atomic force microscopy. Using these tools, Danon patient-derived cardiac tissue, primary fibroblasts, and human induced pluripotent stem cells differentiated into cardiomyocytes (hiPSC-CMs) were analyzed. Metabolic profiling indicated LAMP-2 deficiency promoted a switch toward glycolysis accompanied by rerouting of tryptophan metabolism. Cardiomyocytes’ energetic balance and NAD+/NADH ratio appeared to be maintained despite mitochondrial aging. In turn, metabolic adaption was accompanied by a senescence-associated signature. Similarly, Danon fibroblasts appeared more stress prone and less biomechanically compliant. Overall, shaping of both morphology and metabolism contributed to the loss of cardiac biomechanical competence that characterizes the clinical progression of Danon disease. Full article
(This article belongs to the Special Issue Clinical and Research of Genetic Cardiomyopathies)
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25 pages, 4279 KiB  
Article
Microbial Dynamics between Yeasts and Acetic Acid Bacteria in Kombucha: Impacts on the Chemical Composition of the Beverage
by Thierry Tran, Cosette Grandvalet, François Verdier, Antoine Martin, Hervé Alexandre and Raphaëlle Tourdot-Maréchal
Foods 2020, 9(7), 963; https://doi.org/10.3390/foods9070963 - 21 Jul 2020
Cited by 111 | Viewed by 13678
Abstract
Kombucha is a traditional low-alcoholic beverage made from sugared tea and transformed by a complex microbial consortium including yeasts and acetic acid bacteria (AAB). To study the microbial interactions and their impact on the chemical composition of the beverage, an experimental design with [...] Read more.
Kombucha is a traditional low-alcoholic beverage made from sugared tea and transformed by a complex microbial consortium including yeasts and acetic acid bacteria (AAB). To study the microbial interactions and their impact on the chemical composition of the beverage, an experimental design with nine couples associating one yeast strain and one AAB strain isolated from original black tea kombucha was set up. Three yeast strains belonging to the genera Brettanomyces, Hanseniaspora, and Saccharomyces and three strains of Acetobacter and Komagataeibacter species were chosen. Monocultures in sugared tea were analyzed to determine their individual microbial behaviors. Then, cultivation of the original kombucha consortium and cocultures in sugared tea were compared to determine the interactive microbial effects during successive phases in open and closed incubation conditions. The results highlight the main impact of yeast metabolism on the product’s chemical composition and the secondary impact of bacterial species on the composition in organic acids. The uncovered microbial interactions can be explained by different strategies for the utilization of sucrose. Yeasts and AAB unable to perform efficient sucrose hydrolysis rely on yeasts with high invertase activity to access released monosaccharides. Moreover, the presence of AAB rerouted the metabolism of Saccharomyces cerevisiae towards higher invertase and fermentative activities. Full article
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12 pages, 1484 KiB  
Article
Metabolic Landscape of a Genetically Engineered Mouse Model of IDH1 Mutant Glioma
by Victor Ruiz-Rodado, Tomohiro Seki, Tyrone Dowdy, Adrian Lita, Meili Zhang, Sue Han, Chunzhang Yang, Murali K. Cherukuri, Mark R. Gilbert and Mioara Larion
Cancers 2020, 12(6), 1633; https://doi.org/10.3390/cancers12061633 - 19 Jun 2020
Cited by 11 | Viewed by 6268
Abstract
Understanding the metabolic reprogramming of aggressive brain tumors has potential applications for therapeutics as well as imaging biomarkers. However, little is known about the nutrient requirements of isocitrate dehydrogenase 1 (IDH1) mutant gliomas. The IDH1 mutation involves the acquisition of a neomorphic enzymatic [...] Read more.
Understanding the metabolic reprogramming of aggressive brain tumors has potential applications for therapeutics as well as imaging biomarkers. However, little is known about the nutrient requirements of isocitrate dehydrogenase 1 (IDH1) mutant gliomas. The IDH1 mutation involves the acquisition of a neomorphic enzymatic activity which generates D-2-hydroxyglutarate from α-ketoglutarate. In order to gain insight into the metabolism of these malignant brain tumors, we conducted metabolic profiling of the orthotopic tumor and the contralateral regions for the mouse model of IDH1 mutant glioma; as well as to examine the utilization of glucose and glutamine in supplying major metabolic pathways such as glycolysis and tricarboxylic acid (TCA). We also revealed that the main substrate of 2-hydroxyglutarate is glutamine in this model, and how this re-routing impairs its utilization in the TCA. Our 13C tracing analysis, along with hyperpolarized magnetic resonance experiments, revealed an active glycolytic pathway similar in both regions (tumor and contralateral) of the brain. Therefore, we describe the reprogramming of the central carbon metabolism associated with the IDH1 mutation in a genetically engineered mouse model which reflects the tumor biology encountered in glioma patients. Full article
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18 pages, 6351 KiB  
Article
Restoration of Physiological Levels of Uric Acid and Ascorbic Acid Reroutes the Metabolism of Stored Red Blood Cells
by Manon Bardyn, Jingkui Chen, Michaël Dussiot, David Crettaz, Lucas Schmid, Emmanuel Längst, Pascal Amireault, Jean-Daniel Tissot, Mario Jolicoeur and Michel Prudent
Metabolites 2020, 10(6), 226; https://doi.org/10.3390/metabo10060226 - 29 May 2020
Cited by 19 | Viewed by 3445
Abstract
After blood donation, the red blood cells (RBCs) for transfusion are generally isolated by centrifugation and then filtrated and supplemented with additive solution. The consecutive changes of the extracellular environment participate to the occurrence of storage lesions. In this study, the hypothesis is [...] Read more.
After blood donation, the red blood cells (RBCs) for transfusion are generally isolated by centrifugation and then filtrated and supplemented with additive solution. The consecutive changes of the extracellular environment participate to the occurrence of storage lesions. In this study, the hypothesis is that restoring physiological levels of uric and ascorbic acids (major plasmatic antioxidants) might correct metabolism defects and protect RBCs from the very beginning of the storage period, to maintain their quality. Leukoreduced CPD-SAGM RBC concentrates were supplemented with 416 µM uric acid and 114 µM ascorbic acid and stored during six weeks at 4 °C. Different markers, i.e., haematological parameters, metabolism, sensitivity to oxidative stress, morphology and haemolysis were analyzed. Quantitative metabolomic analysis of targeted intracellular metabolites demonstrated a direct modification of several metabolite levels following antioxidant supplementation. No significant differences were observed for the other markers. In conclusion, the results obtained show that uric and ascorbic acids supplementation partially prevented the metabolic shift triggered by plasma depletion that occurs during the RBC concentrate preparation. The treatment directly and indirectly sustains the antioxidant protective system of the stored RBCs. Full article
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15 pages, 1130 KiB  
Article
The Absence of Pyruvate Kinase Affects Glucose-Dependent Carbon Catabolite Repression in Bacillus subtilis
by Joana Sousa, Philipp Westhoff, Karen Methling and Michael Lalk
Metabolites 2019, 9(10), 216; https://doi.org/10.3390/metabo9100216 - 4 Oct 2019
Cited by 13 | Viewed by 4634
Abstract
Pyruvate is a key intermediate of diverse metabolic pathways of central carbon metabolism. In addition to being the end product of glycolysis, pyruvate is an essential carbon distribution point to oxidative metabolism, amino acid and fatty acid syntheses, and overflow metabolite production. Hence, [...] Read more.
Pyruvate is a key intermediate of diverse metabolic pathways of central carbon metabolism. In addition to being the end product of glycolysis, pyruvate is an essential carbon distribution point to oxidative metabolism, amino acid and fatty acid syntheses, and overflow metabolite production. Hence, a tight regulation of pyruvate kinase (Pyk) activity is of great importance. This study aimed to analyze targeted metabolites from several pathways and possible changes in Bacillus subtilis lacking Pyk. Wild type and Δpyk cells were cultivated in chemically defined medium with glucose and pyruvate as carbon sources, and the extracted metabolites were analyzed by 1H-NMR, GC-MS, HPLC-MS, and LC-MS/MS. The results showed that the perturbation created in the pyruvate node drove an adaptation to new conditions by altering the nutritional compounds’ consumption. In Δpyk, pyruvate, which is subject to glucose-dependent carbon catabolite repression, did not comply with the hierarchy in carbon source utilization. Other metabolic alterations were observed such as the higher secretion of the overflow metabolites acetoin and 2,3-butanediol by Δpyk. Our results help to elucidate the regulatory transport of glucose and pyruvate in B. subtilis and possible metabolic reroute to alternative pathways in the absence of Pyk. Full article
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16 pages, 1352 KiB  
Review
Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy
by Mònica Zamora and Josep A. Villena
Int. J. Mol. Sci. 2019, 20(11), 2833; https://doi.org/10.3390/ijms20112833 - 11 Jun 2019
Cited by 64 | Viewed by 9029
Abstract
Diabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the [...] Read more.
Diabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the underlying cause of DCMremains to be unveiled. Several pathogenic factors, including glucose and lipid toxicity, mitochondrial dysfunction, increased oxidative stress, sustained activation of the renin-angiotensin system (RAS) or altered calcium homeostasis, have been shown to contribute to the structural and functional alterations that characterize diabetic hearts. However, all these pathogenic mechanisms appear to stem from the metabolic inflexibility imposed by insulin resistance or lack of insulin signaling. This results in absolute reliance on fatty acids for the synthesis of ATP and impairment of glucose oxidation. Glucose is then rerouted to other metabolic pathways, with harmful effects on cardiomyocyte function. Here, we discuss the role that impaired cardiac insulin signaling in diabetic or insulin-resistant individuals plays in the onset and progression of DCM. Full article
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23 pages, 818 KiB  
Review
Advances in Metabolic Engineering of Cyanobacteria for Photosynthetic Biochemical Production
by Martin C. Lai and Ethan I. Lan
Metabolites 2015, 5(4), 636-658; https://doi.org/10.3390/metabo5040636 - 27 Oct 2015
Cited by 84 | Viewed by 11064
Abstract
Engineering cyanobacteria into photosynthetic microbial cell factories for the production of biochemicals and biofuels is a promising approach toward sustainability. Cyanobacteria naturally grow on light and carbon dioxide, bypassing the need of fermentable plant biomass and arable land. By tapping into the central [...] Read more.
Engineering cyanobacteria into photosynthetic microbial cell factories for the production of biochemicals and biofuels is a promising approach toward sustainability. Cyanobacteria naturally grow on light and carbon dioxide, bypassing the need of fermentable plant biomass and arable land. By tapping into the central metabolism and rerouting carbon flux towards desirable compound production, cyanobacteria are engineered to directly convert CO2 into various chemicals. This review discusses the diversity of bioproducts synthesized by engineered cyanobacteria, the metabolic pathways used, and the current engineering strategies used for increasing their titers. Full article
(This article belongs to the Special Issue Metabolic Engineering and Synthetic Biology)
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