Differential effect of simvastatin on activation of Rac1 vs. activation of the heat shock protein 27-mediated pathway upon oxidative stress, in human smooth muscle cells
article
In the present study, we have analyzed the response of human smooth muscle cell (SMC)s to oxidative stress, in terms of recruitment of key elements of the stress-activated protein kinase (SAPK) pathway, such as Rac1, p38, and the small heat shock protein (HSP)27. The level of expression of three small HSPs, αB-crystallin, HSP20, HSP27, as well as the phosphorylation levels of HSP27 and p38, were higher in cultured, asynchronously growing SMCs originating from left interior mammary artery (LIMA) than those originating from aorta, saphenous vein, and umbilical vein, validating the choice of SMCs from LIMA as a model system in our study. In synchronized, quiescent SMCs from LIMA, oxidative stress (H2O2 stimulation)-induced membrane translocation of Rac1, p38 phosphorylation, membrane translocation, and phosphorylation of HSP27. In these cells, simvastatin (S), an HMG-CoA reductase inhibitor, blocked, in a mevalonate-dependent way, oxidative stress-induced membrane translocation of Rac1. However, S pretreatment prior to oxidative stress increased the levels of p38 phosphorylation, HSP27 membrane translocation/phosphorylation, actin polymerization, and apoptosis in these cells, in a mevalonate-dependent way. These results establish that S pretreatment has a stimulatory effect on the stress-activated p38/HSP27 pathway, despite its blocking effect on Rac1 activation. © 2002 Elsevier Science Inc. All rights reserved.
Chemicals/CAS: Anticholesteremic Agents; Heat-Shock Proteins; HSPB1 protein, human; Mitogen-Activated Protein Kinases, EC 2.7.1.37; Neoplasm Proteins; p38 Mitogen-Activated Protein Kinases, EC 2.7.1.37; rac1 GTP-Binding Protein, EC 3.6.5.2; Simvastatin, 79902-63-9
Chemicals/CAS: Anticholesteremic Agents; Heat-Shock Proteins; HSPB1 protein, human; Mitogen-Activated Protein Kinases, EC 2.7.1.37; Neoplasm Proteins; p38 Mitogen-Activated Protein Kinases, EC 2.7.1.37; rac1 GTP-Binding Protein, EC 3.6.5.2; Simvastatin, 79902-63-9
Topics
TNO Identifier
236779
ISSN
00062952
Source
Biochemical Pharmacology, 64(10), pp. 1483-1491.
Pages
1483-1491
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