Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway

Abstract Background Intestinal ischemia/reperfusion (I/R) injury commonly occurs during perioperative periods, resulting in high morbidity and mortality on a global scale. Dexmedetomidine (Dex) is a selective α2-agonist that is frequently applied during perioperative periods for its analgesia effect...

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Autores principales:	Qin Zhang, Xiao-Ming Liu, Qian Hu, Zheng-Ren Liu, Zhi-Yi Liu, Huai-Gen Zhang, Yuan-Lu Huang, Qiu-Hong Chen, Wen-Xiang Wang, Xue-Kang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Intestinal ischemia/reperfusion injury Dexmedetomidine Enteric glial cells Mitochondria damage Apoptosis Medicine R
Acceso en línea:	https://doaj.org/article/3750b758684f4261b250b532b1bfc6e8
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spelling	oai:doaj.org-article:3750b758684f4261b250b532b1bfc6e82021-11-14T12:08:21ZDexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway10.1186/s12967-021-03027-61479-5876https://doaj.org/article/3750b758684f4261b250b532b1bfc6e82021-11-01T00:00:00Zhttps://doi.org/10.1186/s12967-021-03027-6https://doaj.org/toc/1479-5876Abstract Background Intestinal ischemia/reperfusion (I/R) injury commonly occurs during perioperative periods, resulting in high morbidity and mortality on a global scale. Dexmedetomidine (Dex) is a selective α2-agonist that is frequently applied during perioperative periods for its analgesia effect; however, its ability to provide protection against intestinal I/R injury and underlying molecular mechanisms remain unclear. Methods To fill this gap, the protection of Dex against I/R injury was examined in a rat model of intestinal I/R injury and in an inflammation cell model, which was induced by tumor necrosis factor-alpha (TNF-α) plus interferon-gamma (IFN-γ) stimulation. Results Our data demonstrated that Dex had protective effects against intestinal I/R injury in rats. Dex was also found to promote mitophagy and inhibit apoptosis of enteric glial cells (EGCs) in the inflammation cell model. PINK1 downregulated p53 expression by promoting the phosphorylation of HDAC3. Further studies revealed that Dex provided protection against experimentally induced intestinal I/R injury in rats, while enhancing mitophagy, and suppressing apoptosis of EGCs through SIRT3-mediated PINK1/HDAC3/p53 pathway in the inflammation cell model. Conclusion Hence, these findings provide evidence supporting the protective effect of Dex against intestinal I/R injury and its underlying mechanism involving the SIRT3/PINK1/HDAC3/p53 axis.Qin ZhangXiao-Ming LiuQian HuZheng-Ren LiuZhi-Yi LiuHuai-Gen ZhangYuan-Lu HuangQiu-Hong ChenWen-Xiang WangXue-Kang ZhangBMCarticleIntestinal ischemia/reperfusion injuryDexmedetomidineEnteric glial cellsMitochondria damageApoptosisMedicineRENJournal of Translational Medicine, Vol 19, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Intestinal ischemia/reperfusion injury Dexmedetomidine Enteric glial cells Mitochondria damage Apoptosis Medicine R
spellingShingle	Intestinal ischemia/reperfusion injury Dexmedetomidine Enteric glial cells Mitochondria damage Apoptosis Medicine R Qin Zhang Xiao-Ming Liu Qian Hu Zheng-Ren Liu Zhi-Yi Liu Huai-Gen Zhang Yuan-Lu Huang Qiu-Hong Chen Wen-Xiang Wang Xue-Kang Zhang Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway
description	Abstract Background Intestinal ischemia/reperfusion (I/R) injury commonly occurs during perioperative periods, resulting in high morbidity and mortality on a global scale. Dexmedetomidine (Dex) is a selective α2-agonist that is frequently applied during perioperative periods for its analgesia effect; however, its ability to provide protection against intestinal I/R injury and underlying molecular mechanisms remain unclear. Methods To fill this gap, the protection of Dex against I/R injury was examined in a rat model of intestinal I/R injury and in an inflammation cell model, which was induced by tumor necrosis factor-alpha (TNF-α) plus interferon-gamma (IFN-γ) stimulation. Results Our data demonstrated that Dex had protective effects against intestinal I/R injury in rats. Dex was also found to promote mitophagy and inhibit apoptosis of enteric glial cells (EGCs) in the inflammation cell model. PINK1 downregulated p53 expression by promoting the phosphorylation of HDAC3. Further studies revealed that Dex provided protection against experimentally induced intestinal I/R injury in rats, while enhancing mitophagy, and suppressing apoptosis of EGCs through SIRT3-mediated PINK1/HDAC3/p53 pathway in the inflammation cell model. Conclusion Hence, these findings provide evidence supporting the protective effect of Dex against intestinal I/R injury and its underlying mechanism involving the SIRT3/PINK1/HDAC3/p53 axis.
format	article
author	Qin Zhang Xiao-Ming Liu Qian Hu Zheng-Ren Liu Zhi-Yi Liu Huai-Gen Zhang Yuan-Lu Huang Qiu-Hong Chen Wen-Xiang Wang Xue-Kang Zhang
author_facet	Qin Zhang Xiao-Ming Liu Qian Hu Zheng-Ren Liu Zhi-Yi Liu Huai-Gen Zhang Yuan-Lu Huang Qiu-Hong Chen Wen-Xiang Wang Xue-Kang Zhang
author_sort	Qin Zhang
title	Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway
title_short	Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway
title_full	Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway
title_fullStr	Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway
title_full_unstemmed	Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway
title_sort	dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via sirt3-dependent pink1/hdac3/p53 pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/3750b758684f4261b250b532b1bfc6e8
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Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway

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