Inhibitory effect of Hsp70 on angiotensin II-induced vascular smooth muscle cell hypertrophy.
Angiotensin II (Ang II), which is an important mediator of both vascular responsiveness and growth, has been shown to induce vascular smooth muscle cell (VSMC) hypertrophy via the activation of a complex series of intracellular signaling events. Heat shock protein 70 (Hsp70) has recently been shown to protect against Ang II-induced hypertension. In this study, we tested the hypothesis that Hsp70 can protect VSMC from Ang II-induced hypertrophy. We treated VSMCs with Ang II to induce hypertrophy and to activate MAPK signaling pathway. We observed that the augmentation of Hsp70 expression inhibited Ang II-stimulated VSMC hypertrophy. This inhibitory effect of Hsp70 appears to be partly due to extracellular signal-regulated kinase (ERK1/2) inactivation, which in turn, may possibly result from the accumulation of MAP kinase phosphatase-1 (MKP-1).
Zheng
Ying
Y
ILCHUN Molecular Medicine Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
Im
Chang-Nim
CN
Seo
Jeong-Sun
JS
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D054638:Dual Specificity Phosphatase 1; D004795:Enzyme Stability / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006984:Hypertrophy; D017874:Immediate-Early Proteins / Q000378:metabolism / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018797:Cell Cycle Proteins; D005419:Flavonoids; D018840:HSP70 Heat-Shock Proteins; D017874:Immediate-Early Proteins; D034741:RNA, Small Interfering; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one