Sustained Ca2 +/calmodulin-dependent kinase II (CaMKII) activation plays a central role in the pathogenesis of a variety of cardiac diseases. Emerging evidence suggests CaMKII evoked programmed cell death, including apoptosis and necroptosis, is one of the key underlying mechanisms for the detrimental effect of sustained CaMKII activation. CaMKII integrates β-adrenergic, Gq coupled receptor, reactive oxygen species (ROS), hyperglycemia, and pro-death cytokine signaling to elicit myocardial apoptosis by intrinsic and extrinsic pathways. New evidence demonstrates CaMKII is also a key mediator of receptor interacting serine/threonine kinase 3 (RIP3)-induced myocardial necroptosis. The role of CaMKII in cell death is dependent upon subcellular localization and varies across isoforms and splice variants. While CaMKII is now an extensively validated nodal signal for promoting cardiac myocyte death, the upstream and downstream pathways and targets remain incompletely understood, demanding further investigation.
- Mitochondrial permeability transition pore
- Oxidized CaMKII
- Programmed cell death
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine