Regulatory role of miR-125a/b in the suppression by selenium of cadmium-induced apoptosis via the mitochondrial pathway in LLC-PK1 cells

• Selenium inhibits cadmium-induced apoptosis in LLC-PK1cells.
• The expression levels of miR-125a/b are reduced by cadmium and increased by selenium.
• Over-expression of miR-125a/b inhibits cadmium-induced apoptosis.
• miR-125a/b regulates the suppression of Cd-induced apoptosis by Se via the mitochondrial pathway.

Cadmium (Cd), a toxic heavy metal, is known to induce kidney damage and renal tubular dysfunction. Our previous studies have indicated that selenium (Se), as an essential trace element, protects against Cd-induced nephrotoxicity via the mitochondrial apoptotic pathway in vivo and in vitro. The available evidence suggests that the expression of miRNAs is altered after Cd exposure. However, the regulatory effects of miRNAs on Cd-induced apoptosis and on the suppression by Se of Cd-induced apoptosis remain unclear. The present study aimed to explore the effects of miRNAs on the suppression by Se of Cd-induced apoptosis in LLC-PK1 cells. miR-125a and miR-125b were downregulated in response to Cd exposure but were upregulated in the Se pretreatment group. Over-expression and low expression of miR-125a/b were simulated by their mimics and inhibitors, respectively. Both Se and over-expression of miR-125a/b attenuated Cd-induced apoptosis through significant enhancement of the anti-apoptotic protein Bcl-2, reduction of the pro-apoptotic proteins Bax and Bak, the release of cytochrome c and the inactivation of caspase-9 and caspase-3. The effects of downregulation of miR-125a/b on apoptosis were similar to those of Cd treatment, and both effects were inhibited by Se. Moreover, miR-125a/b were observed to target Bak and caspase-3 directly. In summary, miR-125a/b play an important role in the suppression of Cd-induced apoptosis by Se via the mitochondrial pathway in LLC-PK1 cells.

Schematic diagram of regulatory role miR-125a/b in the suppression by Se of Cd-induced apoptosis in LLC-PK1 cells. The → indicates induction, and ˧ indicates inhibition.Figure optionsDownload as PowerPoint slide