© 2000 American Heart Association, Inc.
Molecular Medicine |
Mechanical Stress–Induced Heat Shock Protein 70 Expression in Vascular Smooth Muscle Cells Is Regulated by Rac and Ras Small G Proteins but Not Mitogen-Activated Protein Kinases
From the Institute for Biomedical Aging Research (Q.X., C.L., Y.H., G.W.), Austrian Academy of Sciences, Innsbruck, Austria; and the Department of Internal Medicine (G.S.), University Hospital of Vienna, Vienna, Austria.
Correspondence to Dr Qingbo Xu, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail qingbo.xu{at}oeaw.ac.at
Abstract—Previous studies have documented that acute elevation in blood pressure results in heat shock protein (hsp) 70–mRNA expression followed by hsp70-protein production in rat aortas. In this article, we provide evidence that mechanical forces evoke rapid activation of heat shock transcription factor (HSF) and hsp70 accumulation. In our study, Western blot analysis demonstrated that hsp70-protein induction peaked between 6 and 12 hours after treatment with cyclic stain stress (60 cycles/minute, up to 30% elongation). Elevated protein levels were preceded by hsp70-mRNA transcription, which was associated with HSF1 phosphorylation and activation stimulated by mechanical forces, suggesting that the response was regulated at the transcriptional level. Conditioned medium from cyclic strain–stressed vascular smooth muscle cells (VSMCs) did not result in HSF-DNA–binding activation. Furthermore, mitogen-activated protein kinases (MAPKs), including extracellular signal–regulated kinases, c-Jun NH2-terminal protein kinases or stress-activated protein kinases, and p38 MAPKs, were also highly activated in response to cyclic strain stress. Inhibition of extracellular signal–regulated kinase and p38-MAPK activation by their specific inhibitors (PD 98059 and SB 202190) did not influence HSF1 activation. Interestingly, VSMC lines stably expressing dominant-negative rac (rac N17) abolished hsp-protein production and HSF1 activation induced by cyclic strain stress, whereas a significant reduction of hsp70 expression was seen in ras N17–transfected VSMC lines. Thus, our findings demonstrate that cyclic strain stress–induced hsp70 expression is mediated by HSF1 activation and regulated by rac and ras GTP–binding proteins. Induction of hsp70 could be important in maintaining VSMC homeostasis during vascular remodeling in response to hemodynamic stimulation.
Key Words: mechanical stress • smooth muscle cells • heat shock proteins • signaling • G proteins
This article has been cited by other articles:
 |
|
 |
|
  R. Deckers, B. Quesson, J. Arsaut, S. Eimer, F. Couillaud, and C. T. W. Moonen Image-guided, noninvasive, spatiotemporal control of gene expression PNAS, January 27, 2009; 106(4): 1175 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Barutta, S. Pinach, S. Giunti, F. Vittone, J. M. Forbes, R. Chiarle, M. Arnstein, P. C. Perin, G. Camussi, M. E. Cooper, et al. Heat shock protein expression in diabetic nephropathy Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1817 - F1824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-X. Qi, M.-J. Qu, D.-K. Long, B. Liu, Q.-P. Yao, S. Chien, and Z.-L. Jiang Rho-GDP dissociation inhibitor alpha downregulated by low shear stress promotes vascular smooth muscle cell migration and apoptosis: a proteomic analysis Cardiovasc Res, October 1, 2008; 80(1): 114 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Staib, J. C. Quindry, J. P. French, D. S. Criswell, and S. K. Powers Increased temperature, not cardiac load, activates heat shock transcription factor 1 and heat shock protein 72 expression in the heart Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R432 - R439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Dentel, S. G. Blanchard, D. P. Ankrapp, L. R. McCabe, and R. W. Wiseman Inhibition of cross-bridge formation has no effect on contraction-associated phosphorylation of p38 MAPK in mouse skeletal muscle Am J Physiol Cell Physiol, April 1, 2005; 288(4): C824 - C830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Brandes and J. Kreuzer Vascular NADPH oxidases: molecular mechanisms of activation Cardiovasc Res, January 1, 2005; 65(1): 16 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Gregg, F. M. Rauscher, and P. J. Goldschmidt-Clermont Rac regulates cardiovascular superoxide through diverse molecular interactions: more than a binary GTP switch Am J Physiol Cell Physiol, October 1, 2003; 285(4): C723 - C734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Metzler, R. Abia, M. Ahmad, F. Wernig, O. Pachinger, Y. Hu, and Q. Xu Activation of Heat Shock Transcription Factor 1 in Atherosclerosis Am. J. Pathol., May 1, 2003; 162(5): 1669 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Standley, A. Camaratta, B. P. Nolan, C. T. Purgason, and M. A. Stanley Cyclic stretch induces vascular smooth muscle cell alignment via NO signaling Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1907 - H1914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-F. Zhang Vascular adaptation to microgravity: what have we learned? J Appl Physiol, December 1, 2001; 91(6): 2415 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chang, J. S. Wasser, R. N.M. Cornelussen, and A.A. Knowlton Activation of Heat-Shock Factor by Stretch-Activated Channels in Rat Hearts Circulation, July 10, 2001; 104(2): 209 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Han, S. Y. Oh, S. H. Woo, K. H. Kim, J.-H. Kim, H. D. Kim, and H. S. Kang Implication of a Small GTPase Rac1 in the Activation of c-Jun N-terminal Kinase and Heat Shock Factor in Response to Heat Shock J. Biol. Chem., January 12, 2001; 276(3): 1889 - 1895. [Abstract] [Full Text] [PDF]
|
|