Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

Myocardial ischemia or hypoxia can induce myocardial fibroblast proliferation and myocardial fibrosis. Hydrogen sulfide (H<sub>2</sub>S) is a gasotransmitter with multiple physiological functions. In our present study, primary cardiac fibroblasts were incubated with H<sub>2</sub...

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Autores principales:	Yue Zhang, Weiwei Gong, Mengting Xu, Shuping Zhang, Jieru Shen, Mingxian Zhu, Yuqin Wang, Yun Chen, Jiahai Shi, Guoliang Meng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hydrogen sulfide hypoxia cardiac fibroblasts oxidative stress sirtuin 3 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4e32e4b272b64d17b04b26d11a6de22f
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spelling	oai:doaj.org-article:4e32e4b272b64d17b04b26d11a6de22f2021-11-11T17:18:39ZNecroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 310.3390/ijms2221118931422-00671661-6596https://doaj.org/article/4e32e4b272b64d17b04b26d11a6de22f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11893https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Myocardial ischemia or hypoxia can induce myocardial fibroblast proliferation and myocardial fibrosis. Hydrogen sulfide (H<sub>2</sub>S) is a gasotransmitter with multiple physiological functions. In our present study, primary cardiac fibroblasts were incubated with H<sub>2</sub>S donor sodium hydrosulfide (NaHS, 50 μM) for 4 h followed by hypoxia stimulation (containing 5% CO<sub>2</sub> and 1% O<sub>2</sub>) for 4 h. Then, the preventive effects on cardiac fibroblast proliferation and the possible mechanisms were investigated. Our results showed that NaHS reduced the cardiac fibroblast number, decreased the hydroxyproline content; inhibited the EdU positive ratio; and down-regulated the expressions of α-smooth muscle actin (α-SMA), the antigen identified by monoclonal antibody Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III, suggesting that hypoxia-induced cardiac fibroblasts proliferation was suppressed by NaHS. NaHS improved the mitochondrial membrane potential and attenuated oxidative stress, and inhibited dynamin-related protein 1 (DRP1), but enhanced optic atrophy protein 1 (OPA1) expression. NaHS down-regulated receptor interacting protein kinase 1 (RIPK1) and RIPK3 expression, suggesting that necroptosis was alleviated. NaHS increased the sirtuin 3 (SIRT3) expressions in hypoxia-induced cardiac fibroblasts. Moreover, after SIRT3 siRNA transfection, the inhibitory effects on cardiac fibroblast proliferation, oxidative stress, and necroptosis were weakened. In summary, necroptosis inhibition by exogenous H<sub>2</sub>S alleviated hypoxia-induced cardiac fibroblast proliferation via SIRT3.Yue ZhangWeiwei GongMengting XuShuping ZhangJieru ShenMingxian ZhuYuqin WangYun ChenJiahai ShiGuoliang MengMDPI AGarticlehydrogen sulfidehypoxiacardiac fibroblastsoxidative stresssirtuin 3Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11893, p 11893 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydrogen sulfide hypoxia cardiac fibroblasts oxidative stress sirtuin 3 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	hydrogen sulfide hypoxia cardiac fibroblasts oxidative stress sirtuin 3 Biology (General) QH301-705.5 Chemistry QD1-999 Yue Zhang Weiwei Gong Mengting Xu Shuping Zhang Jieru Shen Mingxian Zhu Yuqin Wang Yun Chen Jiahai Shi Guoliang Meng Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3
description	Myocardial ischemia or hypoxia can induce myocardial fibroblast proliferation and myocardial fibrosis. Hydrogen sulfide (H<sub>2</sub>S) is a gasotransmitter with multiple physiological functions. In our present study, primary cardiac fibroblasts were incubated with H<sub>2</sub>S donor sodium hydrosulfide (NaHS, 50 μM) for 4 h followed by hypoxia stimulation (containing 5% CO<sub>2</sub> and 1% O<sub>2</sub>) for 4 h. Then, the preventive effects on cardiac fibroblast proliferation and the possible mechanisms were investigated. Our results showed that NaHS reduced the cardiac fibroblast number, decreased the hydroxyproline content; inhibited the EdU positive ratio; and down-regulated the expressions of α-smooth muscle actin (α-SMA), the antigen identified by monoclonal antibody Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), collagen I, and collagen III, suggesting that hypoxia-induced cardiac fibroblasts proliferation was suppressed by NaHS. NaHS improved the mitochondrial membrane potential and attenuated oxidative stress, and inhibited dynamin-related protein 1 (DRP1), but enhanced optic atrophy protein 1 (OPA1) expression. NaHS down-regulated receptor interacting protein kinase 1 (RIPK1) and RIPK3 expression, suggesting that necroptosis was alleviated. NaHS increased the sirtuin 3 (SIRT3) expressions in hypoxia-induced cardiac fibroblasts. Moreover, after SIRT3 siRNA transfection, the inhibitory effects on cardiac fibroblast proliferation, oxidative stress, and necroptosis were weakened. In summary, necroptosis inhibition by exogenous H<sub>2</sub>S alleviated hypoxia-induced cardiac fibroblast proliferation via SIRT3.
format	article
author	Yue Zhang Weiwei Gong Mengting Xu Shuping Zhang Jieru Shen Mingxian Zhu Yuqin Wang Yun Chen Jiahai Shi Guoliang Meng
author_facet	Yue Zhang Weiwei Gong Mengting Xu Shuping Zhang Jieru Shen Mingxian Zhu Yuqin Wang Yun Chen Jiahai Shi Guoliang Meng
author_sort	Yue Zhang
title	Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3
title_short	Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3
title_full	Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3
title_fullStr	Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3
title_full_unstemmed	Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3
title_sort	necroptosis inhibition by hydrogen sulfide alleviated hypoxia-induced cardiac fibroblasts proliferation via sirtuin 3
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4e32e4b272b64d17b04b26d11a6de22f
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Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

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