{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:30:01Z","timestamp":1789194601091,"version":"build-2803163510"},"reference-count":40,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,7]]},"abstract":"<jats:p>G\u03b1<jats:sub>q<\/jats:sub>protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in cardiac hypertrophy. DAG kinase (DGK) catalyzes DAG phosphorylation and controls cellular DAG levels, thus acting as a regulator of GPCR signaling. It has been reported that DGK\u03b5 acts specifically on DAG produced by inositol cycling. In this study, we examined whether DGK\u03b5 prevents cardiac hypertrophy and progression to heart failure under chronic pressure overload. We generated transgenic mice with cardiac-specific overexpression of DGK\u03b5 (DGK\u03b5-TG) using an \u03b1-myosin heavy chain promoter. There were no differences in cardiac morphology and function between wild-type (WT) and DGK\u03b5-TG mice at the basal condition. Either continuous phenylephrine infusion or thoracic transverse aortic constriction (TAC) was performed in WT and DGK\u03b5-TG mice. Increases in heart weight after phenylephrine infusion and TAC were abolished in DGK\u03b5-TG mice compared with WT mice. Cardiac dysfunction after TAC was prevented in DGK\u03b5-TG mice, and the survival rate after TAC was higher in DGK\u03b5-TG mice than in WT mice. Phenylephrine- and TAC-induced DAG accumulation, the translocation of PKC isoforms, and the induction of fetal genes were blocked in DGK\u03b5-TG mouse hearts. The upregulation of transient receptor potential channel (TRPC)-6 expression after TAC was attenuated in DGK\u03b5-TG mice. In conclusion, these results demonstrate the first evidence that DGK\u03b5 restores cardiac dysfunction and improves survival under chronic pressure overload by controlling cellular DAG levels and TRPC-6 expression. DGK\u03b5 may be a novel therapeutic target to prevent cardiac hypertrophy and progression to heart failure.<\/jats:p>","DOI":"10.1152\/ajpheart.00066.2008","type":"journal-article","created":{"date-parts":[[2008,5,17]],"date-time":"2008-05-17T01:09:25Z","timestamp":1210986565000},"page":"H245-H255","source":"Crossref","is-referenced-by-count":44,"title":["Diacylglycerol kinase-\u03b5 restores cardiac dysfunction under chronic pressure overload: a new specific regulator of G\u03b1<sub>q<\/sub>signaling cascade"],"prefix":"10.1152","volume":"295","author":[{"given":"Takeshi","family":"Niizeki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuchika","family":"Takeishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Kitahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Arimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsunori","family":"Ishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Bilim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Arimoto T, Takeishi Y, Takahashi H, Shishido T, Niizeki T, Koyama Y, Shiga R, Nozaki N, Nakajima O, Nishimaru K, Abe J, Endoh M, Walsh RA, Goto K, Kubota I.Cardiac-specific overexpression of diacylglycerol kinase zeta prevents Gq protein-coupled receptor agonist-induced cardiac hypertrophy in transgenic mice.Circulation113: 60\u201366, 2006.","DOI":"10.1161\/CIRCULATIONAHA.105.560771"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.659037"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.3.384"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00511-4"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605536200"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(99)00004-3"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.11196"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000105087.79373.17"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1253\/circj.71.276"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00015-6"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910213411706"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.277.6.H2298"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000035397.73223.CE"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2007.05.002"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27702"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005313222203"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13893"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00529.2006"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601417"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Otani H, Otani H, Das DK.Alpha 1-adrenoceptor-mediated phosphoinositide breakdown and inotropic response in rat left ventricular papillary muscles.Circ Res62: 8\u201317, 1998.","DOI":"10.1161\/01.RES.62.1.8"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00442.2005"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.51.36181"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2004.01.014"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000016165.23795.1F"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.3.424"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Shubeita HE, McDonough PM, Harris AN, Knowlton KU, Glembotski CC, Brown JH, Chien KR.Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy.J Biol Chem265: 20555\u201320562, 1990.","DOI":"10.1016\/S0021-9258(17)30538-0"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606894103"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000159339.00703.22"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1161\/hh1501.094185"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2709"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.3.264"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.12.1218"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.17.11447"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100814200"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.3.H1079"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R600003-JLR200"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108522"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.04.094"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705133200"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25330"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00066.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T20:52:08Z","timestamp":1631307128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00066.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,7]]}},"alternative-id":["10.1152\/ajpheart.00066.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00066.2008","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7]]}}}