p38δ genetic ablation protects female mice from anthracycline cardiotoxicity
Sharon A. George, Alexi Kiss, Sofian N. Obaid, Aileen Venegas, Trisha Talapatra, Chapman Wei, Tatiana Efimova, Igor R. Efimov
Abstract
This study for the first time identifies the sex-specific roles of the alternative p38γ and p38δ MAPK isoforms in promoting doxorubicin (DOX) cardiotoxicity. We show that p38δ and p38γ/δ systemic deletion was cardioprotective in female but not in male mice. Cardiac structure and function were preserved in DOX-treated p38δ −/− females, and autophagy marker was increased.
Topics & Concepts
CardiotoxicityAutophagyAnthracyclineDoxorubicinp38 mitogen-activated protein kinasesMedicineGene isoformInternal medicinePharmacologyBiologyEndocrinologyCancer researchMAPK/ERK pathwayChemotherapyCell biologyCancerApoptosisGeneticsKinaseBreast cancerGeneChemotherapy-induced cardiotoxicity and mitigationPARP inhibition in cancer therapyCardiac electrophysiology and arrhythmias