Autophagy Attenuates MnCl2-induced Apoptosis in Human Bronchial Epithelial Cells.

Zhun Yuan; Xian Ping Ying; Wei Jian Zhong; Shi Min Tian; Yu Wang; Yong Rui Jia; Wen Chen; Juan Ling FU; Peng Zhao; Zong Can Zhou

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Autophagy Attenuates MnCl2-induced Apoptosis in Human Bronchial Epithelial Cells.

Author: Zhun YUAN ^{1
,

2} ; Xian Ping YING ³ ; Wei Jian ZHONG ³ ; Shi Min TIAN ⁴ ; Yu WANG ¹ ; Yong Rui JIA ⁵ ; Wen CHEN ⁶ ; Juan Ling FU ⁷ ; Peng ZHAO ¹ ; Zong Can ZHOU ⁷
Author Information

1. Department of Toxicology, Peking University Health Science Center, Beijing 100191, China
2. Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Peking University Health Science Center, Beijing 100191, China.
3. Department of Toxicology, Shanghai Municipal Center for Disease Control & Prevention, Shanghai 200336, China.
4. Chinese Academy of Inspection and Quarantine Comprehensive Test Center, Beijing 100123, China.
5. Medical and Healthy Analytical Center, Peking University Health Science Center, Beijing 100191, China.
6. Department of Toxicology, Faculty of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
7. Department of Toxicology, Peking University Health Science Center, Beijing 100191, China.
Publication Type:Journal Article
Keywords: 16HBE cells; Apoptosis; Autophagy; Manganese chloride; Mitochondrial membrane potential
MeSH: Amino Acid Chloromethyl Ketones; pharmacology; Apoptosis; drug effects; Autophagy; drug effects; physiology; Bronchi; Cell Line; Chlorides; pharmacology; Down-Regulation; Epithelial Cells; drug effects; Gene Expression Regulation; drug effects; Humans; Manganese Compounds; pharmacology
From: Biomedical and Environmental Sciences 2016;29(7):494-504
CountryChina
Language:English
Abstract:
OBJECTIVETo investigate the role of autophagy in MnCl2-induced apoptosis in human bronchial epithelial 16HBE cells.
METHODSCell proliferation was measured by MTT assay. Mitochondrial membrane potential (MMP) and apoptosis were measured by flow cytometry. Autophagic vacuoles were detected by fluorescence microscopy. Cellular levels of apoptosis and autophagy-related proteins were measured by western blotting.
RESULTS16HBE cell proliferation was inhibited by MnCl2 in a dose- and time-dependent manner. MnCl2-induced 16HBE cell growth inhibition was related to MMP depolarization prior to the induction of apoptosis. Our data revealed that MnCl2-induced apoptosis in 16HBE cells was mediated by decreased expression of Bcl-2 and increased levels of cleaved caspase-3. It was observed that when we exposed 16HBE cells to MnCl2 in a dose-dependent manner, the formation of autophagic vacuoles and the levels of LC-3B-II were elevated. RNA interference of LC3B in these MnCl2-exposed cells demonstrated that MMP loss and apoptosis were enhanced. Additionally, the pan-caspase inhibitor Z-VAD-FMK increased the cellular levels of Bcl-2 and decreased apoptosis, but did not affect the cellular levels of LC3B in MnCl2-treated 16HBE cells.
CONCLUSIONMnCl2 dose- and time-dependently inhibits 16HBE cell proliferation and induces MMP loss and apoptosis. Autophagy acts in a protective role against MnCl2-induced apoptosis in 16HBE cells.