Liu Pengli, Guo Chen, Cui Yilong, Zhang Xuliang, Xiao Bonan, Liu Menglin, Song Miao, Li Yanfei
Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
J Inorg Biochem. 2022 May;230:111765. doi: 10.1016/j.jinorgbio.2022.111765. Epub 2022 Feb 14.
Aluminum (Al) induces apoptosis via oxidative stress and/or mitochondrial damage. Kidney is the main organ of Al excretion, but whether Al causes apoptosis in kidney of mice remains unclear. Mitophagy maintains cell homeostasis via clearing damaged mitochondria and reducing oxidative stress, but the role in kidney damage caused by Al has also not been investigated. In this study, firstly, forty wild type (WT) male C57 mice were randomly exposed to AlCl at 0, 44.825, 89.65 or 179.3 mg/kg body weight in drinking water for 90 days, respectively. Our results confirmed that Al induced apoptosis, and activated PINK1 (phosphatase and tensin homolog (PTEN)-induced putative kinase1)/Parkin (E3 ubiquitin ligase PARK2)-mediated mitophagy with the dose increased. And secondly, to further assess the role of PINK1/Parkin-mediated mitophagy in Al-induced kidney damage, twenty Parkin knockout (Parkin) mice and twenty WT mice were divided into WT group, WT + Al group, Parkin group, and Parkin + Al group, and they were provided with AlCl at a dose of 0 or 179.3 mg/kg body weight in drinking water for 90 days, respectively. The results showed that Parkin induced more severe kidney injury caused by Al. Besides, Parkin aggravated oxidative stress and apoptosis caused by Al. Overall, our findings indicate that the activation of PINK1/Parkin-mediated mitophagy protects against apoptosis in kidney damage caused by Al.
铝（Al）通过氧化应激和/或线粒体损伤诱导细胞凋亡。肾脏是铝排泄的主要器官，但铝是否会导致小鼠肾脏细胞凋亡仍不清楚。线粒体自噬通过清除受损线粒体和减轻氧化应激来维持细胞内环境稳定，但铝所致肾脏损伤中线粒体自噬的作用尚未得到研究。在本研究中，首先，将40只野生型（WT）雄性C57小鼠分别随机暴露于饮用水中含0、44.825、89.65或179.3mg/kg体重的氯化铝中90天。我们的结果证实，铝诱导细胞凋亡，并随着剂量增加激活磷酸酶和张力蛋白同源物（PTEN）诱导的假定激酶1（PINK1）/Parkin（E3泛素连接酶PARK2）介导的线粒体自噬。其次，为了进一步评估PINK1/Parkin介导的线粒体自噬在铝诱导的肾脏损伤中的作用，将20只Parkin基因敲除（Parkin-/-）小鼠和20只WT小鼠分为WT组、WT+Al组、Parkin-/-组和Parkin-/-+Al组，分别给予饮用水中剂量为0或179.3mg/kg体重的氯化铝90天。结果表明，Parkin-/-使铝所致的肾脏损伤更严重。此外，Parkin-/-加重了铝所致的氧化应激和细胞凋亡。总体而言，我们的研究结果表明，PINK1/Parkin介导的线粒体自噬的激活可保护小鼠免受铝所致肾脏损伤中的细胞凋亡。
