Caveolin-1 Expression by Means of P38beta Mitogen-activated Protein Kinase Mediates the Antiproliferative Effect of Carbon Monoxide

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Jul 30

PMID 16051704

Citations 50

Authors

Hong Pyo Kim

Xue Wang

Atsunori Nakao

Sung Il Kim

Noriko Murase

Mary E Choi

Stefan W Ryter

Augustine M K Choi

Affiliations

Soon will be listed here.

Abstract

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 MAPK. p38beta-/- fibroblasts did not induce caveolin-1 in response to CO, and exhibited a diminished basal caveolin-1 expression, which was restored by p38beta gene transfer. p38beta 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 p38beta 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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