endothelin-1 and monodansylcadaverine

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.

Topics: Animals; Animals, Newborn; Cadaverine; Cells, Cultured; Cystamine; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin-1; Enzyme Inhibitors; GTP Phosphohydrolases; GTP-Binding Proteins; Hypertrophy; Myocytes, Cardiac; Protein Glutamine gamma Glutamyltransferase 2; Rats; Rats, Wistar; Receptor, Endothelin A; RNA, Messenger; Transglutaminases