© 2000 American Heart Association, Inc.
ATVB Electronic Pages |
ATVB Online Only
March 2000
ATVB is pleased to announce that some articles will now be published online only. Articles published online only will undergo the same review process as papers in the printed journal. Publication online only will allow those articles to be published more rapidly and also will allow the journal to publish more papers.
Articles published online will be identified by (
) in the Table
of Contents. The abstract will be published in the print issue, and the
full-length article can be accessed at www.atvbaha.org. Articles
will be cited in the same way as other papers and will be indexed in
MEDLINE, Index Medicus, and other indexing services.
We anticipate that online only publication, after a rigorous review process, will grow rapidly. We will appreciate feedback and suggestions from readers and authors during the early months of this experiment.
Ras/Rac-Dependent Activation of p38 Mitogen-Activated Protein Kinases in Smooth Muscle Cells Stimulated by Cyclic Strain Stress
Chaohong Li, Yanhua Hu, Gertraud Sturm, Georg Wick, Qingbo Xu
Abstract—p38, a subfamily of the mitogen-activated protein kinases (MAPKs), is a crucial signal transducer between a variety of extracellular stimuli and gene expression in mammalian cells. This kinase is activated in cultured cells stimulated by heat shock, osmotic stress, and proinflammatory cytokines, but a similar activation of p38 MAPKs in vascular smooth muscle cells (SMCs) stimulated by mechanical stress has yet to be studied. We studied signal pathways leading to time- and strength-dependent p38 activation in rat SMCs in response to cyclic strain stress. p38 phosphorylation in stressed SMCs showed maximal activation at 10 minutes. This activation was significantly inhibited by pretreatment of the SMCs with pertussis toxin, a G-protein antagonist, and enhanced by treatment with suramin, a growth factor receptor antagonist, but opposite effects in the activation of extracellular signal–regulated kinases stimulated by mechanical forces were found. p38 activation was markedly reduced in stressed SMCs after protein kinase C depletion. Interestingly, SMC lines stably expressing dominant-negative ras (ras N17) or rac1 (rac1 N17) almost abolished p38 phosphorylation induced by cyclic strain stress. When p38 activation was inhibited by the specific inhibitor SB 202190, SMC migration, determined in a Boyden chamber in response to stimulation with platelet-derived growth factor-BB, and SMC proliferation, stimulated by cyclic strain stress, were abrogated. Thus, we provide the first evidence that cyclic strain stress rapidly activates p38 MAPKs via activation of protein kinase C ras/rac signal pathways, suggesting that p38 MAPKs are important signal transducers mediating the mechanical stress–induced cell responses essential for SMC migration and proliferation. (Arterioscler Thromb Vasc Biol. 2000;20:e1-e9.)
Key Words: mechanical stress p38 mitogen-activated protein kinase G proteins vascular smooth muscle cells signal transduction
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