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Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation
Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cystein...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641705/ https://www.ncbi.nlm.nih.gov/pubmed/37922764 http://dx.doi.org/10.1016/j.redox.2023.102949 |
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author | Alam, Shafiul Pardue, Sibile Shen, Xinggui Glawe, John D. Yagi, Takashi Bhuiyan, Mohammad Alfrad Nobel Patel, Rakesh P. Dominic, Paari S. Virk, Chiranjiv S. Bhuiyan, Md Shenuarin Orr, A. Wayne Petit, Chad Kolluru, Gopi K. Kevil, Christopher G. |
author_facet | Alam, Shafiul Pardue, Sibile Shen, Xinggui Glawe, John D. Yagi, Takashi Bhuiyan, Mohammad Alfrad Nobel Patel, Rakesh P. Dominic, Paari S. Virk, Chiranjiv S. Bhuiyan, Md Shenuarin Orr, A. Wayne Petit, Chad Kolluru, Gopi K. Kevil, Christopher G. |
author_sort | Alam, Shafiul |
collection | PubMed |
description | Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress. |
format | Online Article Text |
id | pubmed-10641705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-106417052023-11-14 Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation Alam, Shafiul Pardue, Sibile Shen, Xinggui Glawe, John D. Yagi, Takashi Bhuiyan, Mohammad Alfrad Nobel Patel, Rakesh P. Dominic, Paari S. Virk, Chiranjiv S. Bhuiyan, Md Shenuarin Orr, A. Wayne Petit, Chad Kolluru, Gopi K. Kevil, Christopher G. Redox Biol Research Paper Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress. Elsevier 2023-10-30 /pmc/articles/PMC10641705/ /pubmed/37922764 http://dx.doi.org/10.1016/j.redox.2023.102949 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Alam, Shafiul Pardue, Sibile Shen, Xinggui Glawe, John D. Yagi, Takashi Bhuiyan, Mohammad Alfrad Nobel Patel, Rakesh P. Dominic, Paari S. Virk, Chiranjiv S. Bhuiyan, Md Shenuarin Orr, A. Wayne Petit, Chad Kolluru, Gopi K. Kevil, Christopher G. Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation |
title | Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation |
title_full | Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation |
title_fullStr | Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation |
title_full_unstemmed | Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation |
title_short | Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation |
title_sort | hypoxia increases persulfide and polysulfide formation by amp kinase dependent cystathionine gamma lyase phosphorylation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641705/ https://www.ncbi.nlm.nih.gov/pubmed/37922764 http://dx.doi.org/10.1016/j.redox.2023.102949 |
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