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10.2174/1381612826666200806101137 http://scihub22266oqcxt.onion/10.2174/1381612826666200806101137 32767925!ä!32767925 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Curr+Pharm+Des 2021 ; 27 (5): 595-609 Nephropedia Template TP {{tp|p=32767925|t=2021. Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions |pdf=|usr=}}{{32767925}} gab.com Text Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions JO: Curr Pharm Des http://www.kidney.de/pget.php?&tw=1&pmid=32767925 #FOAvip Molecular hydrogen (H(2)) was long regarded as non-functional in mammalian cells. We overturned the concept by demonstrating that H(2) exhibits antioxidant effects and protects cells against oxidative stress. Subsequently, it has been revealed that H(2) has multiple functions in addition to antioxidant effects, including antiinflammatory, anti-allergic functions, and as cell death and autophagy regulation. Additionally, H(2) stimulates energy metabolism. As H(2) does not readily react with most biomolecules without a catalyst, it is essential to identify the primary targets with which H(2) reacts or interacts directly. As a first event, H(2) may react directly with strong oxidants, such as hydroxyl radicals (*OH) in vivo. This review addresses the key issues related to this in vivo reaction. *OH may have a physiological role because it triggers a free radical chain reaction and may be involved in the regulation of Ca2+- or mitochondrial ATP-dependent K+-channeling. In the subsequent pathway, H(2) suppressed a free radical chain reaction, leading to decreases in lipid peroxide and its end products. Derived from the peroxides, 4-hydroxy-2-nonenal functions as a mediator that up-regulates multiple functional PGC-1alpha. As the other direct target in vitro and in vivo, H(2) intervenes in the free radical chain reaction to modify oxidized phospholipids, which may act as an antagonist of Ca2+-channels. The resulting suppression of Ca2+-signaling inactivates multiple functional NFAT and CREB transcription factors, which may explain H(2) multi-functionality. This review also addresses the involvement of NFAT in the beneficial role of H(2) in COVID-19, Alzheimer's disease and advanced cancer. We discuss some unsolved issues of H(2) action on lipopolysaccharide signaling, MAPK and NF-kappaB pathways and the Nrf2 paradox. Finally, as a novel idea for the direct targeting of H2, this review introduces the possibility that H(2) causes structural changes in proteins via hydrate water changes. Twit Text FOAVip Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions ????Curr Pharm Des http://www.kidney.de/pget.php?&tw=1&pmid=32767925 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32767925 #FOAvip English Wikipedia <ref>{{Cite pmid|32767925}}</ref> Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions #MMPMID32767925 Ohta S Curr Pharm Des 2021[]; 27 (5): 595-609 PMID32767925show ga Molecular hydrogen (H(2)) was long regarded as non-functional in mammalian cells. We overturned the concept by demonstrating that H(2) exhibits antioxidant effects and protects cells against oxidative stress. Subsequently, it has been revealed that H(2) has multiple functions in addition to antioxidant effects, including antiinflammatory, anti-allergic functions, and as cell death and autophagy regulation. Additionally, H(2) stimulates energy metabolism. As H(2) does not readily react with most biomolecules without a catalyst, it is essential to identify the primary targets with which H(2) reacts or interacts directly. As a first event, H(2) may react directly with strong oxidants, such as hydroxyl radicals (*OH) in vivo. This review addresses the key issues related to this in vivo reaction. *OH may have a physiological role because it triggers a free radical chain reaction and may be involved in the regulation of Ca2+- or mitochondrial ATP-dependent K+-channeling. In the subsequent pathway, H(2) suppressed a free radical chain reaction, leading to decreases in lipid peroxide and its end products. Derived from the peroxides, 4-hydroxy-2-nonenal functions as a mediator that up-regulates multiple functional PGC-1alpha. As the other direct target in vitro and in vivo, H(2) intervenes in the free radical chain reaction to modify oxidized phospholipids, which may act as an antagonist of Ca2+-channels. The resulting suppression of Ca2+-signaling inactivates multiple functional NFAT and CREB transcription factors, which may explain H(2) multi-functionality. This review also addresses the involvement of NFAT in the beneficial role of H(2) in COVID-19, Alzheimer's disease and advanced cancer. We discuss some unsolved issues of H(2) action on lipopolysaccharide signaling, MAPK and NF-kappaB pathways and the Nrf2 paradox. Finally, as a novel idea for the direct targeting of H2, this review introduces the possibility that H(2) causes structural changes in proteins via hydrate water changes. |*COVID-19[MESH] |Animals[MESH] |Humans[MESH] |Hydrogen[MESH] |Hydrogen Peroxide[MESH] |Oxidation-Reduction[MESH] |Oxidative Stress[MESH]Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert(epmc).pdf DeepDyve Pubget Overpricing