Persistently increased CaMKIIδ autophosphorylation mediates pathologic SR Ca loss in a murine model of Doxorubicin-induced cardiomyopathy.

ABSTRACT:

Background

Doxorubicin (DOX)-induced cardiomyopathy (DICM) manifests as left ventricular (LV) systolic dysfunction. DOX triggers oxidative stress and CaMKIIδ activity in cardiac myocytes. CaMKIIδ activation leads to impaired intracellular Ca handling and contractile dysfunction because of pathologic Ca loss from the sarcoplasmic reticulum (SR). While CaMKIIδ is canonically activated by autophosphorylation, it can also be activated via oxidation.

Objectives

We aimed to investigate the predominant mode of CaMKIIδ activation in DICM.

Methods

We utilized two transgenic mouse models, one lacking CaMKIIδ (CaMKIIδ^-/-) and a "redox-dead" CaMKIIδ^Val281/282 model. Acute changes in intracellular Ca handling and CaMKIIδ activation status were examined

SUBMITTER: Feder AL 

PROVIDER: S-EPMC12721290 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature