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Overexpression of HO-1 assisted PM2.5-induced apoptosis failure and autophagy-related cell necrosis
- Zhou, Wei, Yuan, Xiaoyan, Zhang, Li, Su, Baoting, Tian, Dongdong, Li, Yang, Zhao, Jun, Wang, Yimei, Peng, Shuangqing
- Ecotoxicology and environmental safety 2017 v.145 pp. 605-614
- acute exposure, air pollution, apoptosis, autophagy, cytosol, cytotoxicity, epithelial cells, heme oxygenase (biliverdin-producing), hospitals, humans, mitochondria, necrosis, particulates, respiratory tract diseases, risk, small interfering RNA, China
- Severe smog/haze events accompanied by extremely high concentrations of airborne fine particulate matter (PM2.5) have emerged frequently in China and the potential health risks have attracted ever-growing attention. During these episodes, a surge in hospital visits for acute respiratory symptoms and respiratory diseases exacerbation has been reported to be associated with acute exposure to high-levels of particulate matters. To investigate cell fate determination and the underlying pathogenic mechanisms during severe haze episodes or smog events, we exposed human lung epithelial cells (BEAS-2B) to PM2.5 (0–400μg/mL) for 24h and found that high doses of PM2.5 caused cell necrosis and autophagy dysfunction, while co-treatment with the autophagy inhibitor 3-MA could partially reduce PM2.5-induced cell necrosis. Exposure to PM2.5 also increased the expression and mitochondrial transposition of heme oxygenase 1 (HO-1), which consequently reduced the release of cytochrome C from mitochondria to cytosol. Knockdown of HO-1 by siRNA attenuated the mitochondrial accumulation of HO-1, reversed HO-1-induced the reduction of cytochrome C release and promoted PM2.5-induced cell apoptosis. In contrast to necrosis, PM2.5-induced autophagy was independent of HO-1. In conclusion, our results demonstrate that acute exposure to high PM2.5 concentrations causes autophagy-related cell necrosis. The decrease in cytochrome C release and apoptosis by upregulation of HO-1 maybe assist PM2.5-induced autophagy-related cell necrosis. Further, this study reveals dual roles for HO-1 in PM2.5-induced cytotoxicity and presents a possible explanation for the onset of acute respiratory symptoms under extreme particulate air pollution.