MitomiR-504 alleviates the copper-induced mitochondria-mediated apoptosis by suppressing Bak1 expression in porcine jejunal epithelial cells

• Published in: The Science of the total environment 2023-02, Vol.858 (Pt 3), p.160157, Article 160157
• Main Authors: Hu, Zhuoying, Linn, Nandar, Li, Quanwei, Zhang, Kai, Liao, Jianzhao, Han, Qingyue, Zhang, Hui, Guo, Jianying, Hu, Lianmei, Pan, Jiaqiang, Li, Ying, Tang, Zhaoxin
• Format: Article
• Language: English
• Subjects: apoptosis; Bak1; bioinformatics; bioluminescence assay; caspase-9; Copper; environment; epithelium; heavy metals; Jejunal epithelial cell; jejunum; microRNA; mitochondria; Mitochondria-mediated apoptosis; MitomiR-504; pollutants; swine; transfection
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2022.160157

Copper (Cu), an environmental heavy metal pollutant, has been widely researched in its toxicology. Recently, an increasing number of mitochondrial microRNAs (mitomiRs) have been shown to involve in the metabolic regulation. However, the underlying mechanisms of mitomiRs on regulating apoptosis under Cu exposure are still unclear. Here, we proved that Cu induced mitochondria-mediated apoptosis in porcine jejunal epithelial cells, concomitant with distinct reduction of mitomiR-504 in vivo and in vitro. The miR-504 mimic notably enhanced the mRNA and protein expressions of Bak1, Bax, Cleaved-caspase3 and Caspase-9, and significantly decreased the apoptosis rate and Bcl-2 mRNA and protein levels, indicating that overexpression of mitomiR-504 attenuated the Cu-induced mitochondria-mediated apoptosis. Besides, Bak1 was confirmed as a direct target of mitomiR-504 by the bioinformatics analysis and dual-luciferase reporter assay. Subsequently, transfection of siRNA targeting Bak1 significantly enhanced the alleviating effect of miR-504 mimic on the Cu-induced mitochondria-mediated apoptosis. Overall, these suggested that overexpression of mitomiR-504 alleviated the Cu-induced mitochondria-mediated apoptosis in jejunal epithelial cells by suppressing Bak1 expression. These findings are conducive to elucidating the mechanism of Cu-induced jejunal epithelial pathologies, providing a new research idea for the Cu toxicology. Cu is an environmental heavy metal contaminant. Whereas, mitomiR-504-Bak1 axis can alleviate the Cu-induced mitochondria-mediated apoptosis, which provides a new idea for ecological risk assessment of Cu. [Display omitted] •Cu induced mitochondria-mediated apoptosis in jejunal epithelial cells.•MitomiR-504 alleviated mitochondria-mediated apoptosis.•Bak1 is a direct target of mitomiR-504.•MitomiR-504 inhibited the expression of Bak1.•MitomiR-504 alleviated Cu-induced mitochondria-mediated apoptosis by targeting Bak1.