Heme oxygenase-1 regulates autophagy through carbon-oxygen to alleviate deoxynivalenol-induced hepatic damage

被引:32
作者
Peng, Zhao [1 ,2 ]
Liao, Yuxiao [1 ,2 ]
Wang, Xiaoqian [1 ,2 ]
Chen, Liangkai [1 ,2 ]
Wang, Liangliang [1 ,2 ]
Qin, Chenyuan [1 ,2 ]
Wang, Zhenting [1 ,2 ]
Cai, Mengyao [1 ,2 ]
Hu, Jiawei [1 ,2 ]
Li, Dan [1 ,2 ]
Yao, Ping [1 ,2 ]
Nuessler, Andreas K. [3 ]
Liu, Liegang [1 ,2 ]
Yang, Wei [1 ,2 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Nutr & Food Hyg, Hubei Key Lab Food Nutr & Safety, Hangkong Rd 13, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Nutr & Food Hyg,MOE Key Lab Environm & Hlth, 13 Hangkong Rd, Wuhan 430030, Peoples R China
[3] Univ Tubingen, BG Trauma Ctr, Dept Traumatol, Schnarrenbergstr 95, D-72076 Tubingen, Germany
关键词
Deoxynivalenol; Heme oxygenase-1; Carbon-oxygen; Liver damage; Autophagy; OXIDATIVE STRESS; SIGNALING PATHWAYS; LIVER; PROTECTS; MONOXIDE; INFLAMMATION; MECHANISMS; INDUCTION; HEPATOCYTES; MODULATION;
D O I
10.1007/s00204-019-02649-6
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Deoxynivalenol (DON) cannot be totally removed due to its stable chemical characteristics and chronic exposure to low doses of DON causes significant toxic effects in humans and animals. However, the potential hazard of such low-dose exposure in target organs still remains not completely understood, especially in liver, which is mainly responsible for detoxification of DON. In the present study, we demonstrated for the first time that estimated human daily DON exposure (25 mu g/kg bw) for 30 and 90 days caused low-grade inflammatory infiltration around hepatic centrilobular veins, elevated systemic IL-1 beta, IL-6 and TNF-alpha and impaired liver function evidenced by increased serum ALT activity. At the molecular level, expressions of autophagy-related proteins as well as Cleaved Caspase-3 and Cleaved Caspase-7 were upregulated during DON exposure, which indicated the activation of autophagy and apoptosis. Importantly, AAV-mediated liver-specific overexpression of HO-1 reversed DON-induced liver damages, upregulated autophagy and attenuated apoptosis in liver, while AAV-mediated HO-1 silence aggravated DON-induced liver damages, inhibited autophagy and increased apoptosis. Furthermore, in vitro experiments demonstrated that lentivirus-mediated HO-1 overexpression in Hepa 1-6 cells prolonged the duration of autophagy and delayed the onset of apoptosis. HO-1 silence in Hepa 1-6 cells inhibited activation of autophagy and accelerated occurrence of apoptosis, and these could be recovered by CO pre-treatment. Therefore, we suppose that HO-1 might be a potential research target to protect human and animal from liver injuries induced by low dose of DON exposure.
引用
收藏
页码:573 / 588
页数:16
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