Blockade of L-type Ca²⁺ channel attenuates doxorubicin-induced cardiomyopathy via suppression of CaMKII-NF-κB pathway.

ABSTRACT: Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-kappa B (NF-κB) play crucial roles in pathogenesis of doxorubicin (DOX)-induced cardiomyopathy. Their activities are regulated by intracellular Ca²⁺. We hypothesized that blockade of L-type Ca²⁺ channel (LTCC) could attenuate DOX-induced cardiomyopathy by regulating CaMKII and NF-κB. DOX activated CaMKII and NF-κB through their phosphorylation and increased cleaved caspase 3 in cardiomyocytes. Pharmacological blockade or gene knockdown of LTCC by nifedipine or small interfering RNA, respectively, suppressed DOX-induced phosphorylation of CaMKII and NF-κB and apoptosis in cardiomyocytes, accompanied by decreasing intracellular Ca²⁺ concentration. Autocamtide 2-related inhibito

SUBMITTER: Ikeda S 

PROVIDER: S-EPMC6614470 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature