title: CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
abstract: 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.
authors.affiliation: Department of Medicine/Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: nfeng3@jhmi.edu.
authors.forename: Ning
authors.initials: N
authors.lastname: Feng
authors.affiliation: Department of Medicine/Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Physiology and the Program in Cellular and Molecular Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address: mark.anderson@jhmi.edu.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Anderson
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D042541:Intracellular Space; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009336:Necrosis / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: Apoptosis; CaMKII; Mitochondria; Mitochondrial permeability transition pore; Necroptosis; Oxidized CaMKII; Programmed cell death; RIP3; ROS