详细记录  
题名:Nitric Oxide-Induced Inhibition Of Smooth Muscle Cell Proliferation Involves S-Nitrosation And Inactivation Of RhoA.
作者:Zuckerbraun BS, Stoyanovsky DA, Sengupta R, Shapiro RA, Ozanich BA, Rao J, Barbato JE, Tzeng E.
来源:Am J Physiol Cell Physiol. 2006 Aug 16; [Epub ahead of print]
URL :http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16914531&query_hl=36&itool=pubmed_docsum
日期:061030
摘要:Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.


Abstract
Nitric oxide (NO) acts as a vasoregulatory molecule that inhibits vascular smooth muscle cell (SMC) proliferation. Studies have illustrated that NO inhibits SMC proliferation via the extracellular signal-regulated kinase (ERK) pathway leading to increased protein levels of the cyclin dependent kinase inhibitor p21(waf1/cip1). The ERK pathway can be pro- or anti-proliferative and it has been demonstrated that the activation status of the small GTPase RhoA determines the proliferative fate of ERK signaling, whereby inactivation of RhoA influences ERK signaling to increase p21(waf1/cip1) and inhibit proliferation. The purpose of these investigations was to examine the effect of NO on RhoA activation/s-nitrosation and to test the hypothesis that inhibition of SMC proliferation by NO is dependent on inactivation of RhoA. NO decreases activation of RhoA as demonstrated by RhoA GTP-binding assays, affinity precipitation, and phalloidin staining of the actin cytoskeleton. Additionally, these effects occur independent of cGMP. NO decreases SMC proliferation and gene transfer of constitutively active RhoA (RhoA(63L)) diminished the anti-proliferative effects of NO as determined by thymidine incorporation. Western blots of p21(waf1/cip1) correlated with changes in proliferation. S-Nitrosation of recombinant RhoA protein and immunoprecipitated RhoA was demonstrated by Western blotting for nitrosocysteine and by measurement of NO release. Furthermore, NO decreases GTP loading of recombinant RhoA protein. These findings indicate that inactivation of RhoA plays a role in NO-mediated SMC anti-proliferation and that S-nitrosation is associated with decreased GTP-binding of RhoA. Nitrosation of RhoA and other proteins likely contribute to cGMP-independent effects of NO.

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