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, DGKalpha, epsilon, and zeta are expressed, and DGKzeta is the predominant isoform. DGKzeta inhibits protein kinase C (PKC) activation and subsequent hypertrophic programs in response to endothelin-1 (ET-1) in neonatal rat cardiomyocytes. DGKzeta blocks cardiac hypertrophy induced by G protein-coupled receptor agonists and pressure overload in vivo. DGKzeta 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 DGKzeta may be a new therapeutic target to prevent cardiac hypertrophy and progression to heart failure.
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, Japan. takeishi@med.id.yamagata-u.ac.jp
Yasuchika
Y
Takeishi
Kaoru
K
Goto
Isao
I
Kubota
D000818:Animals; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006984:Hypertrophy / Q000235:genetics / Q000503:physiopathology*; D007527:Isoenzymes; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000473:pathology; D051381:Rats; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology
D007527:Isoenzymes; D019852:Diacylglycerol Kinase