CaMKII orchestrates endoplasmic reticulum stress and apoptosis in doxorubicin-induced cardiotoxicity by regulating the IRE1α/XBP1s pathway.

ABSTRACT: Doxorubicin (Dox), an anthracycline antibiotic with potent antitumor effects, has limited clinical applications due to cumulative cardiotoxicity. Ca²⁺ /calmodulin-dependent protein kinase II (CaMKII) is implicated in the pathological progression of Dox-induced cardiotoxicity. This study examined the hypothesis that CaMKII exacerbates Dox-induced cardiotoxicity by promoting endoplasmic reticulum stress and apoptosis through regulation of the inositol-requiring enzyme 1α (IRE1α)/spliced X-box binding protein 1 (XBP1s) pathway. Our results demonstrated that CaMKII activation and IRE1α/XBP1s pathway were involved in Dox-treated hearts. CaMKII inhibition with KN-93 ameliorated Dox-induced cardiac dysfunction and pathological myocardial changes. In addition, CaMKII inhibition prevente

SUBMITTER: Kong L 

PROVIDER: S-EPMC9575131 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature