Accumulation of molecules involved in alpha1-adrenergic signal within caveolae: caveolin expression and the development of cardiac hypertrophy.
OBJECTIVE
Caveolin, a major protein component of caveolae, is now considered to be an inhibitor of cellular growth and proliferation. In this study, we examined the localization of the molecules involved in alpha1-adrenergic receptor signal relative to that of caveolin in the heart and the changes in caveolin expression during the development of hypertrophy in SHR.


METHODS
We purified the caveolar protein fractions from rat cardiac tissues, H9C2 cells, and rat vascular smooth muscle cells. Using radioligand receptor binding assay and immunoblot analysis, we examined the distribution and the amount of alpha1-AR and caveolin.


RESULTS
Caveolin-3, the alpha1-adrenergic receptor, Gq and PLC-beta subtypes (PLC-beta1, -beta3) were found exclusively in the caveolar fraction in the above tissues. Caveolin-3 were co-immunoprecipitated with alpha1-adrenergic receptor and Gq from the cardiac tissues. The amount of caveolin subtypes expression (caveolin-1 and -3) and the amount of the alpha1-adrenergic receptor were examined in the hearts of SHR and age-matched WKY (4- and 24-weeks-old). The amount of caveolin-3 expression was significantly smaller in SHR at 24-weeks-old than that in SHR at 4-weeks-old and that in WKY at 24-weeks-old.


CONCLUSIONS
The molecules involved in alpha1-adrenergic signaling are confined to the same microdomain as caveolin. A decrease in caveolin-3 expression may play a role in the development of cardiac hypertrophy in SHR, presumably through de-regulating the inhibition of growth signal in the hearts of SHR in the hypertrophic stage.
Fujita
T
T
Department of Medicine and Physiology, Yokohama City University School of Medicine, Yokohama 236, Japan.
Toya
Y
Y
Iwatsubo
K
K
Onda
T
T
Kimura
K
K
Umemura
S
S
Ishikawa
Y
Y
D000704:Analysis of Variance; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism*; D021941:Caveolae / Q000737:chemistry / Q000378:metabolism*; D051242:Caveolin 1; D051244:Caveolin 3; D022461:Caveolins / Q000032:analysis / Q000378:metabolism*; D002458:Cell Fractionation / Q000379:methods; D002460:Cell Line; D002478:Cells, Cultured; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011233:Precipitin Tests; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000032:analysis / Q000378:metabolism
C495537:Cav1 protein, rat; C495549:Cav3 protein, rat; D051242:Caveolin 1; D051244:Caveolin 3; D022461:Caveolins; D018340:Receptors, Adrenergic, alpha-1; D010738:Type C Phospholipases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins