Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chan, Su Jing, Chai, Chou, Lim, Tze Wei, Yamamoto, Mie, Lo, Eng H, Lai, Mitchell Kim Peng, Wong, Peter Tsun Hon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2015
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
_version_ 1782366676872855552
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
work_keys_str_mv AT chansujing cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury
AT chaichou cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury
AT limtzewei cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury
AT yamamotomie cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury
AT loengh cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury
AT laimitchellkimpeng cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury
AT wongpetertsunhon cystathioninebsynthaseinhibitionisapotentialtherapeuticapproachtotreatmentofischemicinjury