title: Involvement of tissue transglutaminase in endothelin 1-induced hypertrophy in cultured neonatal rat cardiomyocytes.
abstract: A potential link between tissue-type transglutaminase (tTG) and cardiac hypertrophy was suggested recently. However, whether tTG is implicated in hypertrophic agonist-induced cardiac hypertrophy is not yet known. The purpose of this study was to investigate the effects of tTG on cardiomyocyte hypertrophy induced by endothelin (ET) 1. Real-time quantitative RT-PCR and Western blot analysis demonstrated that ET-1 increased the expression of tTG mRNA and protein in cardiomyocytes by activating ET(A) receptors. ET-1 failed to cause increases in cell size and [(3)H]leucine uptake, sarcomere reorganization, and gene induction of the atrial natriuretic factor when cardiomyocytes were treated with monodansylcadaverine, a competitive inhibitor of tTG. Furthermore, the effects of ET-1 on multifunctional activities of tTG were determined by evaluating the incorporation of [(3)H]putrescine into N,N'-dimethylated casein and charcoal absorption, respectively. The results showed that ET-1 did not influence the basal transglutaminase activity of cardiomyocytes but significantly inhibited the 0.1-mmol/L Ca(2+)-stimulated transglutaminase activity. Otherwise, ET-1 elevated the activity of GTPase in a concentration- and time-dependent manner. In vivo, right ventricular hypertrophy induced by 2 weeks of chronic hypoxia was depressed by the tTG inhibitor cystamine (10 to 30 mg/kg, 2 times per day, IP) in a dose-dependent manner. Taken together, our data strongly supported the notion that tTG may act as a positive regulator of the hypertrophic program in response to ET-1. This is probably attributable to the signaling activity of tTG rather than transglutaminase activity.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wei
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Meng
authors.forename: Mu-Gen
authors.initials: MG
authors.lastname: Chi
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Yan
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Ma
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Jia
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Yan
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D003538:Cystamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C008542:monodansylcadaverine; D002103:Cadaverine; D003538:Cystamine