Open AccessCaveolin‐3 inhibits growth signal in cardiac myoblasts in a Ca 2+ ‐dependent manner
Author(s) -
Fujita Takayuki,
Otsu Kouji,
Oshikawa Jin,
Hori Hideaki,
Kitamura Hitoshi,
Ito Takaaki,
Umemura Satoshi,
Minamisawa Susumu,
Ishikawa Yoshihiro
Publication year - 2006
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2006.tb00302.x
Subject(s) - caveolae , caveolin 1 , caveolin , biology , myocyte , microbiology and biotechnology , protein kinase c , signal transduction , calphostin c , calcineurin , medicine , transplantation
Caveolin, a major protein component of caveolae, directly interacts with multiple signaling molecules, such as Ras and growth factor receptors, and inhibits their function. However, the role of the second messenger system in mediating this inhibition by caveolin remains poorly understood. We examined the role of Ca 2+ ‐dependent signal in caveloin‐mediated growth inhibition using a rat cardiac myoblast cell line (H9C2), in which the expression of caveolin‐3, the muscle specific subtype, can be induced using the LacSwitch system. Upon induction with IPTG and serum‐starvation, the expression of caveolin‐3 was increased by 3.3‐fold relative to that of mock‐induced cells. The recombinant caveolin‐3 was localized to the same subcellular fraction as endogenous caveolin‐3 after sucrose gradient purification. Angiotensin II enhanced ERK phosphorylation, but this enhancement was significantly decreased in caveolin‐3‐induced cells in comparison to that in mock‐induced cells. Similarly, when cells were stimulated with fetal calf serum, DNA synthesis, as determined by [ 3 H]‐thymidine incorporation, was significantly decreased in caveolin‐3‐induced cells. When cells were treated with Ca 2+ chelator (BAPTA and EGTA), however, this attenuation was blunted. Calphostin (PKC inhibitor), but not cyclosporine A treatment (calcineurin inhibitor), blunted this attenuation in caveolin‐3 induced cells. Our findings suggest that caveolin exhibits growth inhibition in a Ca 2+ ‐dependent manner, most likely through PKC, in cardiac myoblasts.