Caveolin-1 expression by means of p38β mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide

被引：101

作者：

Kim, HP

Wang, X

Nakao, A

Kim, SI

Murase, N

Choi, ME

Ryter, SW

Choi, AMK

机构：

[1] Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Dept Med, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Sch Med, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15213 USA

[3] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 32期

关键词：

D O I：

10.1073/pnas.0501345102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

During vascular injury, the proliferation and migration of smooth muscle cells leads to characteristic neointima formation, which can be exacerbated by genetic depletion of caveolin-1 or heme oxygenase 1 (HO-1), and inhibited by carbon monoxide (CO), a by-product of heme oxygenase 1 activity. CO inhibited smooth muscle cell proliferation by activating p38 mitogen-activated protein kinase (MAPK) and p21(Waf1/Cip1). Exposure to CO increased caveolin-1 expression in neointimal lesions of injured aorta and in vitro by activating guanylyl cyclase and p38 MAPIK. p38 beta(-/-) fibroblasts did not induce caveolin-1 in response to CO, and exhibited a diminished basal caveolin-1 expression, which was restored by p38 beta gene transfer. p38 beta MAPK down-regulated extracellular signal-regulated protein kinase 1/2 (ERK-1/2), which can repress caveolin-1 transcription. Genetic depletion of caveolin-1 abolished the antiproliferative effect of CO. Thus, we demonstrate that CO, by activating p38 beta MAPK, up-regulates caveolin-1, which acts as a tumor suppressor protein that mediates the growth inhibitory properties of this gas.

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页码：11319 / 11324

页数：6

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