β-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells

In this study, we used human renal cortical epithelial (HRCE) cells. The anti-apoptotic effect of βOHB was evaluated using flow cytometry analysis. The expression of apoptosis-related proteins and HDACs was evaluated by western immunoblot.Key findingsThe results showed that βOHB significantly reduced cisplatin-induced apoptosis in HRCE cells. Furthermore, βOHB significantly reduced cisplatin-induced cleavage of caspase-3, acetylation of histone H3, and phosphorylation of AMP-activated kinase. This anti-apoptotic effect of βOHB was markedly attenuated by an inhibitor of HDAC4/5, and βOHB-mediated suppression of cleavage of caspase3 was significantly blocked by siRNA-induced gene silencing of HDAC5.SignificanceβOHB attenuates cisplatin-induced apoptosis by activation of HDAC5 in HRCE cells, suggesting that βOHB may be a new therapeutic agent for cisplatin nephropathy.
Source: Life Sciences - Category: Biology Source Type: research