期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 230, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2022.111765
关键词
Aluminum; Kidney; Parkin; Mitophagy; Apoptosis
资金
- National Natural Science Foundation of China [31872530]
The study found that aluminum induces apoptosis in kidney cells of mice and activates PINK1/Parkin-mediated mitophagy. Parkin knockout mice showed more severe kidney damage caused by aluminum, suggesting that reduced mitophagy exacerbates oxidative stress and apoptosis in this context.
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 AlCl3 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 AlCl3 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.
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