帕金
粒体自噬
品脱1
化学
谷胱甘肽
肿瘤坏死因子α
巨噬细胞极化
砷
细胞生物学
癌症研究
生物化学
生物
巨噬细胞
免疫学
自噬
细胞凋亡
医学
内科学
酶
疾病
有机化学
帕金森病
体外
作者
Gaoyang Qu,Zi Li,Jiaxin Zhang,Yong Guo,Hui Li,Ruijie Qu,Wei Su,Huan Zhang,Lin Zhang,Hong Xu,Fuhai Shen,Shiang‐Huei Jiang,Heliang Liu,Jinlong Li
出处
期刊:Molecules
[MDPI AG]
日期:2022-12-13
卷期号:27 (24): 8862-8862
被引量:4
标识
DOI:10.3390/molecules27248862
摘要
Inorganic arsenic is a well-known environmental toxicant and carcinogen, and there is overwhelming evidence for an association between this metalloid poisoning and hepatic diseases. However, the biological mechanism involved is not well characterized. In the present study, we probed how inorganic arsenic modulates the hepatic polarization of macrophages, as well as roles of PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy participates in regulating the metalloid-mediated macrophage polarization. Our results indicate that acute arsenic exposure induced macrophage polarization with up-regulated gene expression of inducible nitric oxide synthase (Inos) and arginase-1 (Arg1), monocyte chemotactic protein-1 (Mcp-1) and macrophage inflammatory protein-2 (Mip-2), tumor necrosis factor (Tnf)-α, interleukin (Il)-1β and Il-6, as well as anti-inflammatory factors Il-4 and Il-10. In parallel, we demonstrated the disrupted hepatic redox balance typically characterized by the up-regulation of hydrogen peroxide (H2O2) and glutathione (GSH), and activation of PINK1/Parkin-mediated mitophagy in the livers of acute arsenic-exposed mice. In addition, our results demonstrate that it might be the PINK1/Parkin-mediated mitophagy that renders hepatic macrophage refractory to arsenic-induced up-regulation of the genes Inos, Mcp-1, Mip-2, Tnf-α, Il-1β, Il-6 and Il-4. In this regard, this is the first time the protective effects of PINK1/Parkin-mediated mitophagy in inorganic arsenic-induced hepatic macrophage polarization in vivo have been reported. These findings add novel insights into the arsenical immunotoxicity and provide a basis for the preve.ntive and therapeutic potential of PINK1/Parkin-mediated mitophagy in arsenic poisoning.
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