Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity

Abstract Cell death by hypoxia followed by reoxygenation (H/R) is responsible for tissue injury in multiple pathological conditions. Recent studies found that epigenetic reprogramming mediated by histone deacetylases (HDACs) is implicated in H/R-induced cell death. However, among 18 different isofor...

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Autores principales:	Soon-Duck Ha, Ori Solomon, Masoud Akbari, Alp Sener, Sung Ouk Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c65d5d5d660f401b9720461a75826af9
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spelling	oai:doaj.org-article:c65d5d5d660f401b9720461a75826af92021-12-02T15:07:44ZHistone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity10.1038/s41598-018-29463-x2045-2322https://doaj.org/article/c65d5d5d660f401b9720461a75826af92018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29463-xhttps://doaj.org/toc/2045-2322Abstract Cell death by hypoxia followed by reoxygenation (H/R) is responsible for tissue injury in multiple pathological conditions. Recent studies found that epigenetic reprogramming mediated by histone deacetylases (HDACs) is implicated in H/R-induced cell death. However, among 18 different isoforms comprising 4 classes (I-IV), the role of each HDAC in cell death is largely unknown. This study examined the role of HDAC8, which is the most distinct isoform of class I, in the hypoxia mimetic cobalt- and H/R-induced cytotoxicity of human proximal tubular HK-2 cells. Using the HDAC8-specific activator TM-2-51 (TM) and inhibitor PCI34051, we found that HDAC8 played a protective role in cytotoxicity. TM or overexpression of wild-type HDAC8, but not a deacetylase-defective HDAC8 mutant, prevented mitochondrial fission, loss of mitochondrial transmembrane potential and release of cytochrome C into the cytoplasm. TM suppressed expression of dynamin-related protein 1 (DRP1) which is a key factor required for mitochondrial fission. Suppression of DRP1 by HDAC8 was likely mediated by decreasing the level of acetylated histone H3 lysine 27 (a hallmark of active promoters) at the DRP1 promoter. Collectively, this study shows that HDAC8 inhibits cytotoxicity induced by cobalt and H/R, in part, through suppressing DRP1 expression and mitochondrial fission.Soon-Duck HaOri SolomonMasoud AkbariAlp SenerSung Ouk KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soon-Duck Ha Ori Solomon Masoud Akbari Alp Sener Sung Ouk Kim Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
description	Abstract Cell death by hypoxia followed by reoxygenation (H/R) is responsible for tissue injury in multiple pathological conditions. Recent studies found that epigenetic reprogramming mediated by histone deacetylases (HDACs) is implicated in H/R-induced cell death. However, among 18 different isoforms comprising 4 classes (I-IV), the role of each HDAC in cell death is largely unknown. This study examined the role of HDAC8, which is the most distinct isoform of class I, in the hypoxia mimetic cobalt- and H/R-induced cytotoxicity of human proximal tubular HK-2 cells. Using the HDAC8-specific activator TM-2-51 (TM) and inhibitor PCI34051, we found that HDAC8 played a protective role in cytotoxicity. TM or overexpression of wild-type HDAC8, but not a deacetylase-defective HDAC8 mutant, prevented mitochondrial fission, loss of mitochondrial transmembrane potential and release of cytochrome C into the cytoplasm. TM suppressed expression of dynamin-related protein 1 (DRP1) which is a key factor required for mitochondrial fission. Suppression of DRP1 by HDAC8 was likely mediated by decreasing the level of acetylated histone H3 lysine 27 (a hallmark of active promoters) at the DRP1 promoter. Collectively, this study shows that HDAC8 inhibits cytotoxicity induced by cobalt and H/R, in part, through suppressing DRP1 expression and mitochondrial fission.
format	article
author	Soon-Duck Ha Ori Solomon Masoud Akbari Alp Sener Sung Ouk Kim
author_facet	Soon-Duck Ha Ori Solomon Masoud Akbari Alp Sener Sung Ouk Kim
author_sort	Soon-Duck Ha
title	Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
title_short	Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
title_full	Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
title_fullStr	Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
title_full_unstemmed	Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
title_sort	histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c65d5d5d660f401b9720461a75826af9
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Histone deacetylase 8 protects human proximal tubular epithelial cells from hypoxia-mimetic cobalt- and hypoxia/reoxygenation-induced mitochondrial fission and cytotoxicity

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