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Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury
Hydrogen sulfide (H(2)S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS) has been implicated as the predominant H(2)S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to syn...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397212/ https://www.ncbi.nlm.nih.gov/pubmed/25873304 http://dx.doi.org/10.1177/1759091415578711 |
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author | Chan, Su Jing Chai, Chou Lim, Tze Wei Yamamoto, Mie Lo, Eng H Lai, Mitchell Kim Peng Wong, Peter Tsun Hon |
author_facet | Chan, Su Jing Chai, Chou Lim, Tze Wei Yamamoto, Mie Lo, Eng H Lai, Mitchell Kim Peng Wong, Peter Tsun Hon |
author_sort | Chan, Su Jing |
collection | PubMed |
description | Hydrogen sulfide (H(2)S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS) has been implicated as the predominant H(2)S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H(2)S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H(2)S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H(2)S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment. |
format | Online Article Text |
id | pubmed-4397212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-43972122015-04-16 Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury Chan, Su Jing Chai, Chou Lim, Tze Wei Yamamoto, Mie Lo, Eng H Lai, Mitchell Kim Peng Wong, Peter Tsun Hon ASN Neuro Original Article Hydrogen sulfide (H(2)S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS) has been implicated as the predominant H(2)S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H(2)S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H(2)S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H(2)S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment. SAGE Publications 2015-03-30 /pmc/articles/PMC4397212/ /pubmed/25873304 http://dx.doi.org/10.1177/1759091415578711 Text en © The Author(s) 2015 http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm). |
spellingShingle | Original Article Chan, Su Jing Chai, Chou Lim, Tze Wei Yamamoto, Mie Lo, Eng H Lai, Mitchell Kim Peng Wong, Peter Tsun Hon Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury |
title | Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury |
title_full | Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury |
title_fullStr | Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury |
title_full_unstemmed | Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury |
title_short | Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury |
title_sort | cystathionine β-synthase inhibition is a potential therapeutic approach to treatment of ischemic injury |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397212/ https://www.ncbi.nlm.nih.gov/pubmed/25873304 http://dx.doi.org/10.1177/1759091415578711 |
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