Hebei Key Laboratory for Organ Fibrosis Research, School of Public Health, North China University of Science and Technology, Tangshan 063210, China.
Department of Internal Medicine Nursing, School of Nursing, Wannan Medical College, Wuhu 241000, China.
Molecules. 2022 Dec 13;27(24):8862. doi: 10.3390/molecules27248862.
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 () and arginase-1 (), monocyte chemotactic protein-1 () and macrophage inflammatory protein-2 (), tumor necrosis factor ()-α, interleukin ()-1β and , as well as anti-inflammatory factors and . In parallel, we demonstrated the disrupted hepatic redox balance typically characterized by the up-regulation of hydrogen peroxide (HO) 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 , , , , , and . 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.
无机砷是一种众所周知的环境毒物和致癌物质，有大量证据表明这种类金属中毒与肝脏疾病之间存在关联。然而，其涉及的生物学机制尚未得到很好的描述。在本研究中，我们探讨了无机砷如何调节巨噬细胞的肝脏极化，以及 PTEN 诱导的激酶 1 (PINK1)/Parkin 介导的线粒体自噬在调节类金属介导的巨噬细胞极化中所起的作用。我们的结果表明，急性砷暴露诱导巨噬细胞极化，诱导型一氧化氮合酶 () 和精氨酸酶-1 ()、单核细胞趋化蛋白-1 () 和巨噬细胞炎症蛋白-2 ()、肿瘤坏死因子 ()-α、白细胞介素 ()-1β 和 、以及抗炎因子 和 的基因表达上调。平行地，我们证明了肝脏氧化还原平衡被破坏，通常表现为过氧化氢 (HO) 和谷胱甘肽 (GSH) 的上调，以及急性砷暴露小鼠肝脏中 PINK1/Parkin 介导的线粒体自噬的激活。此外，我们的结果表明，可能是 PINK1/Parkin 介导的线粒体自噬使肝巨噬细胞对砷诱导的基因 、 、 、 、 、 和 上调产生抗性。在这方面，这是首次报道 PINK1/Parkin 介导的线粒体自噬在体内无机砷诱导的肝巨噬细胞极化中的保护作用。这些发现为砷的免疫毒性提供了新的见解，并为预防和治疗砷中毒中 PINK1/Parkin 介导的线粒体自噬提供了依据。
