Open AccessDisruption of the Actin Cytoskeleton Up-Regulates iNOS Expression in Vascular Smooth Muscle Cells
Author(s) -
Yoshiyuki Hattori,
Kikuo Kasai
Publication year - 2004
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200402000-00007
Subject(s) - cytochalasin d , nitric oxide synthase , microbiology and biotechnology , actin , actin cytoskeleton , vascular smooth muscle , cytoskeleton , stress fiber , nitric oxide , cytochalasin , biology , lipopolysaccharide , signal transduction , chemistry , focal adhesion , biochemistry , cell , immunology , endocrinology , smooth muscle
Cytokines and bacterial lipopolysaccharide (LPS) induce the expression of inducible nitric oxide synthase (iNOS), resulting in the release of nitric oxide (NO) from vascular smooth muscle cells. We here demonstrated that disruption of F-actin formation by sequestration of G-actin with the toxin latrunculin B (Lat B) dramatically potentiated LPS-induced iNOS mRNA and protein expression. We also showed that Lat B enhanced interleukin-1beta- andbgr;- and TNFalpha-induced NO production. Lat B by itself had little or no effect on iNOS expression. Cytochalasin D also enhanced LPS-induced NO production. Lat B dose-dependently enhanced LPS-induced iNOS promoter activity but had no effect on the stability of iNOS mRNA. Staining of F-actin with nitrobenzoxadiazole (NBD)-phallacidin demonstrated that Lat B significantly impaired F-actin stress fiber formation. These data indicate that disruption of the actin cytoskeleton up-regulates cytokine-induced iNOS expression via transcriptional regulation. Further analysis of the signaling pathway from the actin cytoskeleton to iNOS expression may yield new insight into the mechanism of iNOS regulation.