Inhibition of Brd4 alleviates renal ischemia/reperfusion injury-induced apoptosis and endoplasmic reticulum stress by blocking FoxO4-mediated oxidative stress.

ABSTRACT: Ischemia/reperfusion injury (I/R) is one of the leading causes of acute kidney injury (AKI) that typically occurs in renal surgeries. However, renal I/R still currently lacks effective therapeutic targets. In this study, we proved that inhibition of Brd4 with its selective inhibitor, JQ1, could exert a protective role in renal I/R injury in mice. Inhibiting Brd4 with either JQ1 or genetic knockdown resulted in reduction of endoplasmic reticulum stress (ERS)-associated protein and proapoptotic protein expression both in I/R-induced injury and hypoxia/reoxygenation (H/R) stimulation in HK-2 cells. H/R-induced apoptosis and ERS depended on oxidative stress in vitro. Moreover, FoxO4, which is involved in the generation of hydrogen peroxide, was up-regulated during H/R stimulation-mediated apop

SUBMITTER: Liu H 

PROVIDER: S-EPMC6475721 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature