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Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury

X-linked inhibitor of apoptosis protein (XIAP) negatively regulates apoptotic pathways at a post-mitochondrial level. XIAP functions by directly binding and inhibiting activation of specific caspases. Upon apoptotic stimuli, mitochondrial second mitochondria-derived activator of caspases (Smac)/dire...

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Autores principales: ZHANG, BAIYU, RONG, RONG, LI, HUIYAN, PENG, XUAN, XIONG, LIPING, WANG, YIHAN, YU, XUEQING, MAO, HAIPING
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270332/
https://www.ncbi.nlm.nih.gov/pubmed/25394481
http://dx.doi.org/10.3892/mmr.2014.2939
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author ZHANG, BAIYU
RONG, RONG
LI, HUIYAN
PENG, XUAN
XIONG, LIPING
WANG, YIHAN
YU, XUEQING
MAO, HAIPING
author_facet ZHANG, BAIYU
RONG, RONG
LI, HUIYAN
PENG, XUAN
XIONG, LIPING
WANG, YIHAN
YU, XUEQING
MAO, HAIPING
author_sort ZHANG, BAIYU
collection PubMed
description X-linked inhibitor of apoptosis protein (XIAP) negatively regulates apoptotic pathways at a post-mitochondrial level. XIAP functions by directly binding and inhibiting activation of specific caspases. Upon apoptotic stimuli, mitochondrial second mitochondria-derived activator of caspases (Smac)/direct IAP-binding protein with low PI (DIABLO) is released into the cytosol, which results in displacement of XIAP from caspases. Heat shock protein 72 (HSP72), an anti-apoptotic protein, prevents mitochondrial injury resulting from acute renal ischemia/reperfusion (I/R), its role in Smac/DIABLO and XIAP signaling remains to be elucidated. In the present study, the hypothesis that HSP72 prevents XIAP degradation in vivo and in vitro was assessed. To this purpose, a rat model of I/R injury was used to investigate the renoprotective role of HSP72 by treatment with geranylgeranylacetone (GGA), a specific inducer of HSP72. The mechanism of the cytoprotective properties of HSP72 was also investigated in vitro using adenovirus-mediated overexpression of HSP72 in adenosine triphosphate (ATP)-depleted human kidney 2 (HK-2) cells. Pre-conditioning rats with GGA attenuated renal tubular cell damage, reduced cell apoptosis, preserved XIAP protein content and improved renal function following I/R injury. An in vitro study was performed in which cells were transiently exposed to 5 mM sodium cyanide in a glucose-free medium in order to induce apoptosis. Compared with the control, overexpression of HSP72 inhibited Smac/DIABLO release from the mitochondria and increased levels of XIAP and pro-caspase 3 in ATP-depleted HK-2 cells. In addition, HSP72 interacted with Smac/DIABLO. The present data demonstrates that HSP72 preserves renal function in I/R injury through its anti-apoptotic effects, which act by suppressing mitochondrial Smac/DIABLO release and preserving XIAP protein content.
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spelling pubmed-42703322014-12-19 Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury ZHANG, BAIYU RONG, RONG LI, HUIYAN PENG, XUAN XIONG, LIPING WANG, YIHAN YU, XUEQING MAO, HAIPING Mol Med Rep Articles X-linked inhibitor of apoptosis protein (XIAP) negatively regulates apoptotic pathways at a post-mitochondrial level. XIAP functions by directly binding and inhibiting activation of specific caspases. Upon apoptotic stimuli, mitochondrial second mitochondria-derived activator of caspases (Smac)/direct IAP-binding protein with low PI (DIABLO) is released into the cytosol, which results in displacement of XIAP from caspases. Heat shock protein 72 (HSP72), an anti-apoptotic protein, prevents mitochondrial injury resulting from acute renal ischemia/reperfusion (I/R), its role in Smac/DIABLO and XIAP signaling remains to be elucidated. In the present study, the hypothesis that HSP72 prevents XIAP degradation in vivo and in vitro was assessed. To this purpose, a rat model of I/R injury was used to investigate the renoprotective role of HSP72 by treatment with geranylgeranylacetone (GGA), a specific inducer of HSP72. The mechanism of the cytoprotective properties of HSP72 was also investigated in vitro using adenovirus-mediated overexpression of HSP72 in adenosine triphosphate (ATP)-depleted human kidney 2 (HK-2) cells. Pre-conditioning rats with GGA attenuated renal tubular cell damage, reduced cell apoptosis, preserved XIAP protein content and improved renal function following I/R injury. An in vitro study was performed in which cells were transiently exposed to 5 mM sodium cyanide in a glucose-free medium in order to induce apoptosis. Compared with the control, overexpression of HSP72 inhibited Smac/DIABLO release from the mitochondria and increased levels of XIAP and pro-caspase 3 in ATP-depleted HK-2 cells. In addition, HSP72 interacted with Smac/DIABLO. The present data demonstrates that HSP72 preserves renal function in I/R injury through its anti-apoptotic effects, which act by suppressing mitochondrial Smac/DIABLO release and preserving XIAP protein content. D.A. Spandidos 2015-03 2014-11-13 /pmc/articles/PMC4270332/ /pubmed/25394481 http://dx.doi.org/10.3892/mmr.2014.2939 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
ZHANG, BAIYU
RONG, RONG
LI, HUIYAN
PENG, XUAN
XIONG, LIPING
WANG, YIHAN
YU, XUEQING
MAO, HAIPING
Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
title Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
title_full Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
title_fullStr Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
title_full_unstemmed Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
title_short Heat shock protein 72 suppresses apoptosis by increasing the stability of X-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
title_sort heat shock protein 72 suppresses apoptosis by increasing the stability of x-linked inhibitor of apoptosis protein in renal ischemia/reperfusion injury
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270332/
https://www.ncbi.nlm.nih.gov/pubmed/25394481
http://dx.doi.org/10.3892/mmr.2014.2939
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