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Keywords = myo-inositol phosphates

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28 pages, 3421 KiB  
Article
The Impact of Nitrogen and Phosphorus Interaction on Growth, Nutrient Absorption, and Signal Regulation in Woody Plants
by Xiaan Tang, Yi Zhang, Panpan Meng, Yingke Yuan, Changhao Li, Xiaotan Zhi and Chunyan Wang
Biology 2025, 14(5), 490; https://doi.org/10.3390/biology14050490 - 30 Apr 2025
Cited by 1 | Viewed by 750
Abstract
This article methodically reveals how, in woody plants (poplar), the interaction between N and P coordinates root structure and nutrient absorption through a complex hormone signaling network. This study bridges a significant gap in our knowledge of nutrient interaction networks. The results demonstrate [...] Read more.
This article methodically reveals how, in woody plants (poplar), the interaction between N and P coordinates root structure and nutrient absorption through a complex hormone signaling network. This study bridges a significant gap in our knowledge of nutrient interaction networks. The results demonstrate that NO3 significantly enhances the gene expression and enzymatic activity of organic acid synthases (MDH, PEPC) and APs. Furthermore, it synergizes with IAA/ABA signals to refine root structure, enhancing the surface area for P absorption. In low Pi availability environments, NO3 further promotes P recycling by simultaneously boosting the levels of Pi transport proteins (notably, the PHO family), facilitating myo-inositol phosphate metabolism (via IMP3/ITPK1-mediated PP-InsPs degradation), and augmenting IAA/SA signals. Pi induces the activity of N assimilation enzymes (GS/GOGAT/GDH), facilitating nitrogen metabolism. However, in the absence of N, it leads to a metabolic imbalance characterized by high enzymatic activity but low efficiency. Alternatively, adequate N availability allows Pi to improve root robustness and N assimilation efficiency, mediated by IAA/GA accumulation and ABA signaling (e.g., SNRK2/ABF). We propose the existence of an intricate network in poplar, orchestrated by transcriptional cascades, metabolic regulation, and hormonal synergism. Key modules such as SPX-PHR, NLA, HHO2, and MYB59 are likely central to this network’s function. These findings offer a foundational framework for the development of molecular breeding and precise fertilization strategies, enhancing the efficient use of N and P in forestry. Full article
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14 pages, 1731 KiB  
Review
Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders
by Chisom J. Onu, Michael Adu, Mohamed Chakkour, Vikalp Kumar and Miriam L. Greenberg
Biomolecules 2025, 15(2), 225; https://doi.org/10.3390/biom15020225 - 4 Feb 2025
Cited by 1 | Viewed by 2450
Abstract
Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, [...] Read more.
Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, metabolic flux, stress response, and other key biological processes. While emerging research has highlighted the significant roles of inositol phosphates in immunity, cancer, and metabolic diseases, there is a lack of comprehensive reviews on their roles in psychiatric and neurological disorders. This review aims to fill that gap by analyzing the existing literature on the importance of inositol phosphates in severe psychiatric and neurological conditions such as Parkinson’s disease, Alzheimer’s disease, bipolar disorder, amyotrophic lateral sclerosis, schizophrenia, and Huntington’s disease, underscoring the potential to pave the way for new treatment regimens for these debilitating disorders targeting inositol pathways. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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28 pages, 2987 KiB  
Review
Towards Improved Bioavailability of Cereal Inositol Phosphates, Myo-Inositol and Phenolic Acids
by Krzysztof Żyła and Aleksandra Duda
Molecules 2025, 30(3), 652; https://doi.org/10.3390/molecules30030652 - 1 Feb 2025
Cited by 2 | Viewed by 1922
Abstract
Cereals are among the foods rich in myo-inositol hexakisphosphate (phytic acid, IP6), lower myo-inositol phosphates (IPx), a wide range of phenolic compounds, as well as vitamins, minerals, oligosaccharides, phytosterols and para-aminobenzoic acid, and are attributed with multiple bioactivities, particularly associated with [...] Read more.
Cereals are among the foods rich in myo-inositol hexakisphosphate (phytic acid, IP6), lower myo-inositol phosphates (IPx), a wide range of phenolic compounds, as well as vitamins, minerals, oligosaccharides, phytosterols and para-aminobenzoic acid, and are attributed with multiple bioactivities, particularly associated with the prevention of metabolic syndrome and colon cancer. The bran fraction of wheat, maize, brown rice and other cereals contains high levels of phytate, free and total phenolics, and endogenous enzymes such as amylases, phytase, xylanase, β-glucanase and feruloyl esterase, whose activities can be increased by germination. The preliminary steps of digestion begin in the oral cavity where substrates for the action of endogenous cereal and salivary enzymes start to be released from the food matrix. IP6 released from phytate complexes with arabinoxylans, starch and protein bodies would eventually enhance the absorption of nutrients, including phenolics, by regulating tight junctions and, together with ferulic acid (FA), would maintain cell barrier integrity and epithelial antibacterial immunity. In addition, both IP6 and FA exert potent and complementary antioxidant effects, while FA together with IPx generated through advanced hydrolysis of IP6 by endogenous and microbial phytases may affect digestive enzyme activity and incretin secretion, resulting in modulated insulin and glucagon release and prevention of various diabetic complications. Contrary to widespread negative attitudes towards phytate, in this review, we present the strategy of selecting cereals with high phytate and phenolic content, as well as high endogenous phytase, feruloyl esterase and endoxylanase activities, to produce value-added health-promoting foods. The advanced hydrolysis of phytate and phenolic compounds by cereal and/or microbial enzymes would generate substantial amounts of “enzymatically generated inositol” (EGI), including IP6, IPx and myo-inositol, the compounds that, together with free FA, provide enhanced bioavailability of cereal nutrients through multiple synergistic effects not previously realised. Full article
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23 pages, 4725 KiB  
Article
Transcriptome and Metabolome Insights into Key Genes Regulating Fat Deposition and Meat Quality in Pig Breeds
by Suthar Teerath Kumar, Yunlong Zheng, Jing Xu, Ziyi Zhao, Qi Zhang, Yunpeng Zhang, Min Li, Hong Zou, Riaz Muhammad Azeem, Wu-Sheng Sun, Yuan Zhao and Shu-Min Zhang
Animals 2024, 14(24), 3560; https://doi.org/10.3390/ani14243560 - 10 Dec 2024
Cited by 4 | Viewed by 1871
Abstract
Meat quality is a complex trait that exhibits significant variation across pig breeds, and the regulatory mechanisms governing pork meat quality are not fully elucidated. We compared the transcriptomics and metabolomics of the longissimus dorsi (LD) muscle between the Songliao Black Pig (SBP) [...] Read more.
Meat quality is a complex trait that exhibits significant variation across pig breeds, and the regulatory mechanisms governing pork meat quality are not fully elucidated. We compared the transcriptomics and metabolomics of the longissimus dorsi (LD) muscle between the Songliao Black Pig (SBP) and Large White × Landrace Pig (LWLDP) to investigate breed-specific differences in meat quality and underlying regulatory pathways. The results showed that SBP meat had a higher marbling score and backfat thickness, a richer color, a lower shear force, and reduced drip loss. Fatty acid (FA) analysis identified 15 significant FAs in the LWLDP, with docosahexaenoic acid (DHA) in the SBP, while amino acid (AA) analysis revealed no breed-based differences. Transcriptome analysis identified 134 upregulated and 362 downregulated genes in the SBP. Protein–protein interaction (PPI) network analysis found 25 key genes, which are associated with muscle development, fat deposition, and overall meat quality, while genes in the insulin signaling pathway, such as PPP1R3B, PPARGC1A, SOCS1, EIF4E, PRKAR2A, PRKAG2, and FASN, play a crucial role in balancing fat metabolism and catabolism. Metabolomic analysis identified 89 upregulated and 10 downregulated metabolites in the SBP, primarily involved in fructose and mannose metabolism, amino acid biosynthesis, nucleotide sugar metabolism, and glucagon signaling pathways. Gene–metabolite association analysis found that the PPP1R3B gene had a strong association with Thr-Leu, Maltol, D-myo-Inositol-4-phosphate, and Fructose-6-phosphate, while MYOG correlated with Mannose-6-phosphate, Fructose-1-phosphate, Mannose-1-phosphate, and Glucose-6-phosphate. In contrast, NR4A3 and PPARGC1A showed a strong negative correlation with most upregulated metabolites. In conclusion, this study identified functional genes, elucidated the mechanisms associated with meat quality traits, and identified gene–metabolite associations involved in energy metabolism, muscle development, and fat deposition, providing valuable insights into the molecular mechanisms that regulate meat quality between pig breeds. Full article
(This article belongs to the Section Pigs)
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19 pages, 552 KiB  
Review
Inositol Hexaphosphate in Bone Health and Disease
by Yuji Yoshiko and Ivana Vucenik
Biomolecules 2024, 14(9), 1072; https://doi.org/10.3390/biom14091072 - 27 Aug 2024
Cited by 1 | Viewed by 2960
Abstract
Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, [...] Read more.
Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, and anticancer) effects on multiple biological processes. Also, IP6 and its metabolites are known to exist in mammalian cells, including human cells, and the role of IP6 as a functional molecule is attracting attention. IP6 can bind to the growth sites of hydroxy-apatite (HA) and calcium oxalate crystals to prevent their growth and hence inhibit pathological calcification. SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone. Full article
(This article belongs to the Special Issue Inositol Phosphates in Health and Disease, 2nd Edition)
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20 pages, 6644 KiB  
Article
Monitoring Fruit Growth and Development in Apricot (Prunus armeniaca L.) through Gene Expression Analysis
by Germán Ortuño-Hernández, María Sánchez, David Ruiz, Pedro Martínez-Gómez and Juan Alfonso Salazar
Int. J. Mol. Sci. 2024, 25(16), 9081; https://doi.org/10.3390/ijms25169081 - 21 Aug 2024
Cited by 1 | Viewed by 1694
Abstract
The main objective of this study was to monitor apricot development and ripening through gene expression analysis of key candidate genes using the RT-qPCR technique. Eight apricot cultivars were selected to analyze phenological and genetic patterns from pre-ripening stages through to postharvest. In [...] Read more.
The main objective of this study was to monitor apricot development and ripening through gene expression analysis of key candidate genes using the RT-qPCR technique. Eight apricot cultivars were selected to analyze phenological and genetic patterns from pre-ripening stages through to postharvest. In addition, 19 selected genes were analyzed in the contrasting cultivars ‘Cebas Red’ and ‘Rojo Pasión’ in different stages (two preharvest stages S1 and S2, one harvest stage S3, and two postharvest stages S4 and S5). This pool of genes included genes related to fruit growth and ripening, genes associated with fruit color, and genes linked to the fruit’s nutraceutical aspects. Among the studied genes, Polygalacturonase (PG), Pectin methylesterase (PME), Aminocyclopropane-1-carboxylate synthase (ACS), and Myo-inositol-1-phosphate synthase (INO1) were directly related to fruit maturation and quality. Significant differential expression was observed between the cultivars, which correlated with variations in firmness, shelf life, and sensory characteristics of the apricots. ‘Rojo Pasión’ displayed high levels of PG, associated with rapid maturation and shorter postharvest shelf life, whereas ‘Cebas Red’ exhibited lower levels of this gene, resulting in greater firmness and extended shelf life. Genes CCD4, CRTZ, and ZDS, related to carotenoids, showed varied expression patterns during growth and postharvest stages, with higher levels in ‘Rojo Pasión’. On the other hand, Sucrose synthase (SUSY) and Lipoxygenase (LOX2) were prominent during the postharvest and growth stages, respectively. Additionally, GDP-L-galactose phosphorylase (VTC2_5) was linked to better postharvest performance. This research provides valuable insights for future breeding initiatives aimed at enhancing the quality and sustainability of apricot cultivation. Full article
(This article belongs to the Special Issue Advances in Research on Fruit Crop Breeding and Genetics: 3rd Edition)
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14 pages, 1676 KiB  
Article
Metabolic Shift in Porcine Spermatozoa during Sperm Capacitation-Induced Zinc Flux
by Tyler Weide, Kayla Mills, Ian Shofner, Matthew W. Breitzman and Karl Kerns
Int. J. Mol. Sci. 2024, 25(14), 7919; https://doi.org/10.3390/ijms25147919 - 19 Jul 2024
Cited by 2 | Viewed by 2134
Abstract
Mammalian spermatozoa rely on glycolysis and mitochondrial oxidative phosphorylation for energy leading up to fertilization. Sperm capacitation involves a series of well-regulated biochemical steps that are necessary to give spermatozoa the ability to fertilize the oocyte. Additionally, zinc ion (Zn2+) fluxes [...] Read more.
Mammalian spermatozoa rely on glycolysis and mitochondrial oxidative phosphorylation for energy leading up to fertilization. Sperm capacitation involves a series of well-regulated biochemical steps that are necessary to give spermatozoa the ability to fertilize the oocyte. Additionally, zinc ion (Zn2+) fluxes have recently been shown to occur during mammalian sperm capacitation. Semen from seven commercial boars was collected and analyzed using image-based flow cytometry before, after, and with the inclusion of 2 mM Zn2+ containing in vitro capacitation (IVC) media. Metabolites were extracted and analyzed via Gas Chromatography-Mass Spectrometry (GC-MS), identifying 175 metabolites, with 79 differentially abundant across treatments (p < 0.05). Non-capacitated samples showed high levels of respiration-associated metabolites including glucose, fructose, citric acid, and pyruvic acid. After 4 h IVC, these metabolites significantly decreased, while phosphate, lactic acid, and glucitol increased (p < 0.05). With zinc inclusion, we observed an increase in metabolites such as lactic acid, glucitol, glucose, fructose, myo-inositol, citric acid, and succinic acid, while saturated fatty acids including palmitic, dodecanoic, and myristic acid decreased compared to 4 h IVC, indicating regulatory shifts in metabolic pathways and fatty acid composition during capacitation. These findings underscore the importance of metabolic changes in improving artificial insemination and fertility treatments in livestock and humans. Full article
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17 pages, 2422 KiB  
Article
Activated Inositol Phosphate, Substrate for Synthesis of Prostaglandylinositol Cyclic Phosphate (Cyclic PIP)—The Key for the Effectiveness of Inositol-Feeding
by Antonios Gypakis, Stephan Adelt, Horst Lemoine, Günter Vogel and Heinrich K. Wasner
Int. J. Mol. Sci. 2024, 25(3), 1362; https://doi.org/10.3390/ijms25031362 - 23 Jan 2024
Cited by 1 | Viewed by 1739
Abstract
The natural cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is biosynthesized from prostaglandin E (PGE) and activated inositol phosphate (n-Ins-P), which is synthesized by a particulate rat-liver-enzyme from GTP and a precursor named inositol phosphate (pr-Ins-P), whose 5-ring phosphodiester structure is essential [...] Read more.
The natural cyclic AMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is biosynthesized from prostaglandin E (PGE) and activated inositol phosphate (n-Ins-P), which is synthesized by a particulate rat-liver-enzyme from GTP and a precursor named inositol phosphate (pr-Ins-P), whose 5-ring phosphodiester structure is essential for n-Ins-P synthesis. Aortic myocytes, preincubated with [3H] myo-inositol, synthesize after angiotensin II stimulation (30 s) [3H] pr-Ins-P (65% yield), which is converted to [3H] n-Ins-P and [3H] cyclic PIP. Acid-treated (1 min) [3H] pr-Ins-P co-elutes with inositol (1,4)-bisphosphate in high performance ion chromatography, indicating that pr-Ins-P is inositol (1:2-cyclic,4)-bisphosphate. Incubation of [3H]-GTP with unlabeled pr-Ins-P gave [3H]-guanosine-labeled n-Ins-P. Cyclic PIP synthase binds the inositol (1:2-cyclic)-phosphate part of n-Ins-P to PGE and releases the [3H]-labeled guanosine as [3H]-GDP. Thus, n-Ins-P is most likely guanosine diphospho-4-inositol (1:2-cyclic)-phosphate. Inositol feeding helps patients with metabolic conditions related to insulin resistance, but explanations for this finding are missing. Cyclic PIP appears to be the key for explaining the curative effect of inositol supplementation: (1) inositol is a molecular constituent of cyclic PIP; (2) cyclic PIP triggers many of insulin’s actions intracellularly; and (3) the synthesis of cyclic PIP is decreased in diabetes as shown in rodents. Full article
(This article belongs to the Special Issue Inositol in Translational Medicine)
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21 pages, 2761 KiB  
Review
The Genetic Background of Abnormalities in Metabolic Pathways of Phosphoinositides and Their Linkage with the Myotubular Myopathies, Neurodegenerative Disorders, and Carcinogenesis
by Maria Derkaczew, Piotr Martyniuk, Robert Hofman, Krzysztof Rutkowski, Adam Osowski and Joanna Wojtkiewicz
Biomolecules 2023, 13(10), 1550; https://doi.org/10.3390/biom13101550 - 19 Oct 2023
Cited by 3 | Viewed by 2137
Abstract
Myo-inositol belongs to one of the sugar alcohol groups known as cyclitols. Phosphatidylinositols are one of the derivatives of Myo-inositol, and constitute important mediators in many intracellular processes such as cell growth, cell differentiation, receptor recycling, cytoskeletal organization, and membrane fusion. They also [...] Read more.
Myo-inositol belongs to one of the sugar alcohol groups known as cyclitols. Phosphatidylinositols are one of the derivatives of Myo-inositol, and constitute important mediators in many intracellular processes such as cell growth, cell differentiation, receptor recycling, cytoskeletal organization, and membrane fusion. They also have even more functions that are essential for cell survival. Mutations in genes encoding phosphatidylinositols and their derivatives can lead to many disorders. This review aims to perform an in-depth analysis of these connections. Many authors emphasize the significant influence of phosphatidylinositols and phosphatidylinositols’ phosphates in the pathogenesis of myotubular myopathies, neurodegenerative disorders, carcinogenesis, and other less frequently observed diseases. In our review, we have focused on three of the most often mentioned groups of disorders. Inositols are the topic of many studies, and yet, there are no clear results of successful clinical trials. Analysis of the available literature gives promising results and shows that further research is still needed. Full article
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14 pages, 5180 KiB  
Article
Transcriptome Analysis Reveals Candidate Genes Involved in Gibberellin-Induced Fruit Development in Rosa roxburghii
by Xiaolong Huang, Xiaoai Wu, Guilian Sun, Yu Jiang and Huiqing Yan
Plants 2023, 12(19), 3425; https://doi.org/10.3390/plants12193425 - 28 Sep 2023
Cited by 7 | Viewed by 1986
Abstract
Gibberellins (GAs) play indispensable roles in the fruit development of horticultural plants. Unfortunately, the molecular basis behind GAs regulating fruit development in R. roxburghii remains obscure. Here, GA3 spraying to R. roxburghii ‘Guinong 5’ at full-bloom promoted fruit size and weight, prickle [...] Read more.
Gibberellins (GAs) play indispensable roles in the fruit development of horticultural plants. Unfortunately, the molecular basis behind GAs regulating fruit development in R. roxburghii remains obscure. Here, GA3 spraying to R. roxburghii ‘Guinong 5’ at full-bloom promoted fruit size and weight, prickle development, seed abortion, ascorbic acid accumulation, and reduction in total soluble sugar. RNA-Seq analysis was conducted to generate 45.75 Gb clean reads from GA3- and non-treated fruits at 120 days after pollination. We obtained 4275 unigenes belonging to differently expressed genes (DEGs). Gene ontology and the Kyoto Encyclopedia of Genes and Genomes displayed that carbon metabolism and oxidative phosphorylation were highly enriched. The increased critical genes of DEGs related to pentose phosphate, glycolysis/gluconeogenesis, and citrate cycle pathways might be essential for soluble sugar degradation. Analysis of DEGs implicated in ascorbate revealed the myoinositol pathway required to accumulate ascorbic acid. Finally, DEGs involved in endogenous phytohormones and transcription factors, including R2R3 MYB, bHLH, and WRKY, were determined. These findings indicated that GA3-trigged morphological alterations might be related to the primary metabolites, hormone signaling, and transcription factors, providing potential candidate genes that could be guided to enhance the fruit development of R. roxburghii in practical approaches. Full article
(This article belongs to the Special Issue Recent Advances in Horticultural Plant Genomics)
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16 pages, 8373 KiB  
Article
γ-Aminobutyric Acid Priming Alleviates Acid-Aluminum Toxicity to Creeping Bentgrass by Regulating Metabolic Homeostasis
by Min Zhou, Yan Yuan, Junnan Lin, Long Lin, Jianzhen Zhou and Zhou Li
Int. J. Mol. Sci. 2023, 24(18), 14309; https://doi.org/10.3390/ijms241814309 - 20 Sep 2023
Cited by 4 | Viewed by 1857
Abstract
Aluminum (Al) toxicity is a major limiting factor for plant growth and crop production in acidic soils. This study aims to investigate the effects of γ-aminobutyric acid (GABA) priming on mitigating acid-Al toxicity to creeping bentgrass (Agrostis stolonifera) associated with changes [...] Read more.
Aluminum (Al) toxicity is a major limiting factor for plant growth and crop production in acidic soils. This study aims to investigate the effects of γ-aminobutyric acid (GABA) priming on mitigating acid-Al toxicity to creeping bentgrass (Agrostis stolonifera) associated with changes in plant growth, photosynthetic parameters, antioxidant defense, key metabolites, and genes related to organic acids metabolism. Thirty-seven-old plants were primed with or without 0.5 mM GABA for three days and then subjected to acid-Al stress (5 mmol/L AlCl3·6H2O, pH 4.35) for fifteen days. The results showed that acid-Al stress significantly increased the accumulation of Al and also restricted aboveground and underground growths, photosynthesis, photochemical efficiency, and osmotic balance, which could be effectively alleviated by GABA priming. The application of GABA significantly activated antioxidant enzymes, including superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, to reduce oxidative damage to cells under acid-Al stress. Metabolomics analysis demonstrated that the GABA pretreatment significantly induced the accumulation of many metabolites such as quinic acid, pyruvic acid, shikimic acid, glycine, threonine, erythrose, glucose-6-phosphate, galactose, kestose, threitol, ribitol, glycerol, putrescine, galactinol, and myo-inositol associated with osmotic, antioxidant, and metabolic homeostases under acid-Al stress. In addition, the GABA priming significantly up-regulated genes related to the transportation of malic acid and citric acid in leaves in response to acid-Al stress. Current findings indicated GABA-induced tolerance to acid-Al stress in relation to scavenging of reactive oxygen species, osmotic adjustment, and accumulation and transport of organic metabolites in leaves. Exogenous GABA priming could improve the phytoremediation potential of perennial creeping bentgrass for the restoration of Al-contaminated soils. Full article
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15 pages, 2455 KiB  
Article
Parkinson’s Disease and the Heart: Studying Cardiac Metabolism in the 6-Hydroxydopamine Model
by Victor Silva da Fonsêca, Valeria de Cassia Goncalves, Mario Augusto Izidoro, Antônio-Carlos Guimarães de Almeida, Fernando Luiz Affonso Fonseca, Fulvio Alexandre Scorza, Josef Finsterer and Carla Alessandra Scorza
Int. J. Mol. Sci. 2023, 24(15), 12202; https://doi.org/10.3390/ijms241512202 - 30 Jul 2023
Cited by 4 | Viewed by 1929
Abstract
Parkinson’s-disease (PD) is an incurable, age-related neurodegenerative disease, and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main [...] Read more.
Parkinson’s-disease (PD) is an incurable, age-related neurodegenerative disease, and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient’s quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD; however, its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine are the metabolites that significantly discriminate parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, the biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, the glucose-alanine cycle, glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation. Full article
(This article belongs to the Section Molecular Neurobiology)
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13 pages, 2465 KiB  
Article
Assigning the Absolute Configuration of Inositol Poly- and Pyrophosphates by NMR Using a Single Chiral Solvating Agent
by Kevin Ritter, Nikolaus Jork, Anne-Sophie Unmüßig, Maja Köhn and Henning J. Jessen
Biomolecules 2023, 13(7), 1150; https://doi.org/10.3390/biom13071150 - 19 Jul 2023
Cited by 5 | Viewed by 2321
Abstract
Inositol phosphates constitute a family of highly charged messenger molecules that play diverse roles in cellular processes. The various phosphorylation patterns they exhibit give rise to a vast array of different compounds. To fully comprehend the biological interconnections, the precise molecular identification of [...] Read more.
Inositol phosphates constitute a family of highly charged messenger molecules that play diverse roles in cellular processes. The various phosphorylation patterns they exhibit give rise to a vast array of different compounds. To fully comprehend the biological interconnections, the precise molecular identification of each compound is crucial. Since the myo-inositol scaffold possesses an internal mirror plane, enantiomeric pairs can be formed. Most commonly employed methods for analyzing InsPs have been geared towards resolving regioisomers, but they have not been capable of resolving enantiomers. In this study, we present a general approach for enantiomer assignment using NMR measurements. To achieve this goal, we used 31P-NMR in the presence of L-arginine amide as a chiral solvating agent, which enables the differentiation of enantiomers. Using chemically synthesized standard compounds allows for an unambiguous assignment of the enantiomers. This method was applied to highly phosphorylated inositol pyrophosphates, as well as to lowly phosphorylated inositol phosphates and bisphosphonate analogs. Our method will facilitate the assignment of biologically relevant isomers when isolating naturally occurring compounds from biological specimens. Full article
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17 pages, 3059 KiB  
Article
Metabolic Fingerprints of Effective Fluoxetine Treatment in the Prefrontal Cortex of Chronically Socially Isolated Rats: Marker Candidates and Predictive Metabolites
by Dragana Filipović, Julica Inderhees, Alexandra Korda, Predrag Tadić, Markus Schwaninger, Dragoš Inta and Stefan Borgwardt
Int. J. Mol. Sci. 2023, 24(13), 10957; https://doi.org/10.3390/ijms241310957 - 30 Jun 2023
Cited by 7 | Viewed by 2215
Abstract
The increasing prevalence of depression requires more effective therapy and the understanding of antidepressants’ mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using [...] Read more.
The increasing prevalence of depression requires more effective therapy and the understanding of antidepressants’ mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography–high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze the metabolomics data, we employed univariate and multivariate analysis and biomarker capacity assessment using the receiver operating characteristic (ROC) curve. We also identified the most predictive biomarkers using a support vector machine with linear kernel (SVM-LK). Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as marker candidates for fluoxetine efficacy. ROC analysis revealed 4 significant marker candidates for CSIS group discrimination, and 10 for fluoxetine efficacy. SVM-LK with accuracies of 61.50% or 93.30% identified a panel of 7 or 25 predictive metabolites for depressive-like behavior or fluoxetine effectiveness, respectively. Overall, metabolic fingerprints combined with the ROC curve and SVM-LK may represent a new approach to identifying marker candidates or predictive metabolites for ongoing disease or disease risk and treatment outcome. Full article
(This article belongs to the Topic Proteomics and Metabolomics in Biomedicine, 2nd Volume)
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20 pages, 1928 KiB  
Review
Cyclitols: From Basic Understanding to Their Association with Neurodegeneration
by Maria Derkaczew, Piotr Martyniuk, Adam Osowski and Joanna Wojtkiewicz
Nutrients 2023, 15(9), 2029; https://doi.org/10.3390/nu15092029 - 23 Apr 2023
Cited by 5 | Viewed by 3024
Abstract
One of the most common cyclitols found in eukaryotic cells—Myo-inositol (MI) and its derivatives play a key role in many cellular processes such as ion channel physiology, signal transduction, phosphate storage, cell wall formation, membrane biogenesis and osmoregulation. The aim of this paper [...] Read more.
One of the most common cyclitols found in eukaryotic cells—Myo-inositol (MI) and its derivatives play a key role in many cellular processes such as ion channel physiology, signal transduction, phosphate storage, cell wall formation, membrane biogenesis and osmoregulation. The aim of this paper is to characterize the possibility of neurodegenerative disorders treatment using MI and the research of other therapeutic methods linked to MI’s derivatives. Based on the reviewed literature the researchers focus on the most common neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Spinocerebellar ataxias, but there are also works describing other seldom encountered diseases. The use of MI, d-pinitol and other methods altering MI’s metabolism, although research on this topic has been conducted for years, still needs much closer examination. The dietary supplementation of MI shows a promising effect on the treatment of neurodegenerative disorders and can be of great help in alleviating the accompanying depressive symptoms. Full article
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