Role of diacylglycerol kinase in cellular regulatory processes: A new regulator for cardiomyocyte hypertrophy

Diacylglycerol (DAG) kinase (DGK) phosphorylates and converts DAG to phosphatidic acid. DGK regulates cellular DAG levels and attenuates DAG signaling. The 10 mammalian DGK isoforms have been identified to date. In cardiac myocytes, DGKα, ε, and ζ are expressed, and DGKζ is the predominant isoform. DGKζ inhibits protein kinase C (PKC) activation and subsequent hypertrophic programs in response to endothelin-1 (ET-1) in neonatal rat cardiomyocytes. DGKζ blocks cardiac hypertrophy induced by G protein-coupled receptor agonists and pressure overload in vivo. DGKζ attenuates ventricular remodeling and improves survival after myocardial infarction. These data provide a novel insight for subcellular mechanisms of cardiac hypertrophy and heart failure, and DGKζ may be a new therapeutic target to prevent cardiac hypertrophy and progression to heart failure.