Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.

<h4>Objective</h4>Mitochondrial oxidative stress is the basis for pancreatic β-cell apoptosis and a common pathway for numerous types of damage, including glucotoxicity and lipotoxicity. We cultivated mice pancreatic β-cell tumor Min6 cell lines in vitro and observed pancreatic β-cell ap...

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Autores principales:	Zhen Li, Zhiguang Zhou, Gan Huang, Fang Hu, Yufei Xiang, Lining He
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18672abc430f4d07bbdcdba2e78468e3
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spelling	oai:doaj.org-article:18672abc430f4d07bbdcdba2e78468e32021-11-18T08:49:41ZExendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.1932-620310.1371/journal.pone.0076172https://doaj.org/article/18672abc430f4d07bbdcdba2e78468e32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204601/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Mitochondrial oxidative stress is the basis for pancreatic β-cell apoptosis and a common pathway for numerous types of damage, including glucotoxicity and lipotoxicity. We cultivated mice pancreatic β-cell tumor Min6 cell lines in vitro and observed pancreatic β-cell apoptosis and changes in mitochondrial function before and after the addition of Exendin-4. Based on these observations, we discuss the protective role of Exendin-4 against mitochondrial oxidative damage and its relationship with Ca(2+)-independent phospholipase A2.<h4>Methods</h4>We established a pancreatic β-cell oxidative stress damage model using Min6 cell lines cultured in vitro with tert-buty1 hydroperoxide and hydrogen peroxide. We then added Exendin-4 to observe changes in the rate of cell apoptosis (Annexin-V-FITC-PI staining flow cytometry and DNA ladder). We detected the activity of the caspase 3 and 8 apoptotic factors, measured the mitochondrial membrane potential losses and reactive oxygen species production levels, and detected the expression of cytochrome c and Smac/DLAMO in the cytosol and mitochondria, mitochondrial Ca2-independent phospholipase A2 and Ca(2+)-independent phospholipase A2 mRNA.<h4>Results</h4>The time-concentration curve showed that different percentages of apoptosis occurred at different time-concentrations in tert-buty1 hydroperoxide- and hydrogen peroxide-induced Min6 cells. Incubation with 100 µmol/l of Exendin-4 for 48 hours reduced the Min6 cell apoptosis rate (p<0.05). The mitochondrial membrane potential loss and total reactive oxygen species levels decreased (p<0.05), and the release of cytochrome c and Smac/DLAMO from the mitochondria was reduced. The study also showed that Ca(2+)-independent phospholipase A2 activity was positively related to Exendin-4 activity.<h4>Conclusion</h4>Exendin-4 reduces Min6 cell oxidative damage and the cell apoptosis rate, which may be related to Ca(2)-independent phospholipase A2.Zhen LiZhiguang ZhouGan HuangFang HuYufei XiangLining HePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76172 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhen Li Zhiguang Zhou Gan Huang Fang Hu Yufei Xiang Lining He Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.
description	<h4>Objective</h4>Mitochondrial oxidative stress is the basis for pancreatic β-cell apoptosis and a common pathway for numerous types of damage, including glucotoxicity and lipotoxicity. We cultivated mice pancreatic β-cell tumor Min6 cell lines in vitro and observed pancreatic β-cell apoptosis and changes in mitochondrial function before and after the addition of Exendin-4. Based on these observations, we discuss the protective role of Exendin-4 against mitochondrial oxidative damage and its relationship with Ca(2+)-independent phospholipase A2.<h4>Methods</h4>We established a pancreatic β-cell oxidative stress damage model using Min6 cell lines cultured in vitro with tert-buty1 hydroperoxide and hydrogen peroxide. We then added Exendin-4 to observe changes in the rate of cell apoptosis (Annexin-V-FITC-PI staining flow cytometry and DNA ladder). We detected the activity of the caspase 3 and 8 apoptotic factors, measured the mitochondrial membrane potential losses and reactive oxygen species production levels, and detected the expression of cytochrome c and Smac/DLAMO in the cytosol and mitochondria, mitochondrial Ca2-independent phospholipase A2 and Ca(2+)-independent phospholipase A2 mRNA.<h4>Results</h4>The time-concentration curve showed that different percentages of apoptosis occurred at different time-concentrations in tert-buty1 hydroperoxide- and hydrogen peroxide-induced Min6 cells. Incubation with 100 µmol/l of Exendin-4 for 48 hours reduced the Min6 cell apoptosis rate (p<0.05). The mitochondrial membrane potential loss and total reactive oxygen species levels decreased (p<0.05), and the release of cytochrome c and Smac/DLAMO from the mitochondria was reduced. The study also showed that Ca(2+)-independent phospholipase A2 activity was positively related to Exendin-4 activity.<h4>Conclusion</h4>Exendin-4 reduces Min6 cell oxidative damage and the cell apoptosis rate, which may be related to Ca(2)-independent phospholipase A2.
format	article
author	Zhen Li Zhiguang Zhou Gan Huang Fang Hu Yufei Xiang Lining He
author_facet	Zhen Li Zhiguang Zhou Gan Huang Fang Hu Yufei Xiang Lining He
author_sort	Zhen Li
title	Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.
title_short	Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.
title_full	Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.
title_fullStr	Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.
title_full_unstemmed	Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.
title_sort	exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic beta cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/18672abc430f4d07bbdcdba2e78468e3
work_keys_str_mv	AT zhenli exendin4protectsmitochondriafromreactiveoxygenspeciesinducedapoptosisinpancreaticbetacells AT zhiguangzhou exendin4protectsmitochondriafromreactiveoxygenspeciesinducedapoptosisinpancreaticbetacells AT ganhuang exendin4protectsmitochondriafromreactiveoxygenspeciesinducedapoptosisinpancreaticbetacells AT fanghu exendin4protectsmitochondriafromreactiveoxygenspeciesinducedapoptosisinpancreaticbetacells AT yufeixiang exendin4protectsmitochondriafromreactiveoxygenspeciesinducedapoptosisinpancreaticbetacells AT lininghe exendin4protectsmitochondriafromreactiveoxygenspeciesinducedapoptosisinpancreaticbetacells
_version_	1718421247634702336

Exendin-4 protects mitochondria from reactive oxygen species induced apoptosis in pancreatic Beta cells.

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