Behavior of caveolae and caveolin-3 during the development of myocyte hypertrophy.
Recent studies have indicated that caveolae are enriched in a variety of signaling molecules, some of which are associated with cardiomyocyte hypertrophy. Caveolin-3, a major constituent of cardiac caveolae, has been suggested to interact with several signaling molecules. We investigated the morphologic changes of caveolae and caveolin-3 expression in hypertrophied cardiomyocytes induced by an alpha1-adrenergic agonist. Cultured rat neonatal cardiomyocytes were used for the experiments. Phenylephrine induced cellular hypertrophy associated with an increase of the number of caveolae and an up-regulation of caveolin-3. Although PMA increased the number of caveolae and the caveolin-3 expression, the extent of these up-regulations was less than that by phenylephrine. Moreover, ionomycin increased the number of caveolae and up-regulated caveolin-3 as much as phenylephrine. Phenylephrine-induced up-regulations of caveolae and caveolin-3 expression were inhibited by BAPTA, suggesting that the intracellular Ca2+ is involved in those regulations. Inhibitors of calcineurin and Ca2+calmodulin-dependent kinase II attenuated the phenylephrine-induced up-regulation of caveolin-3. In pressure-overloaded rat hearts, caveolin-3 protein levels were increased compared with sham-operated rats. In conclusion, the number of caveolae and the expression of caveolin-3 were up-regulated in rat hypertrophied cardiomyocytes, possibly via the alterations of intracellular Ca2+ and protein kinase C.
Kikuchi
Toshio
T
Department of Internal Medicine III and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
Oka
Naoki
N
Koga
Akimasa
A
Miyazaki
Hiroshi
H
Ohmura
Haruya
H
Imaizumi
Tsutomu
T
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000473:pathology*; D021941:Caveolae / Q000473:pathology*; D051244:Caveolin 3; D022461:Caveolins / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D015151:Immunoblotting; D007930:Leucine / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000648:ultrastructure; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; C495549:Cav3 protein, rat; D051244:Caveolin 3; D022461:Caveolins; D015240:Phorbol 12,13-Dibutyrate; D007930:Leucine