Change of mitogen-activated protein kinase phosphatase-1 in heart and aorta of SHR and its effect on proliferation of vascular smooth muscle cells stimulated by angiotensin II.
- Author:
San-Bao CHAI
1
;
Ding-Fang BU
;
Li-Jia TONG
;
Chao-Shu TANG
Author Information
- Publication Type:Journal Article
- MeSH: Angiotensin II; pharmacology; Animals; Aorta; cytology; enzymology; Cell Proliferation; Cells, Cultured; Dual Specificity Phosphatase 1; metabolism; Heart; Hypertension; metabolism; Mitogen-Activated Protein Kinase 3; metabolism; Muscle, Smooth, Vascular; cytology; Myocardium; cytology; enzymology; Myocytes, Smooth Muscle; drug effects; metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY
- From: Chinese Journal of Applied Physiology 2002;18(1):55-58
- CountryChina
- Language:Chinese
-
Abstract:
AIM AND METHODSTo investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP-1) in the regulation of cells proliferation, the expression of MKP-1 and extracellular signal-regulated kinase-1 (ERK-1) in heart and aorta of spontaneous hypertensive rat (SHR) and WKY were studied. We also investigated the effect of MKP-1 genes,which were transfected into vascular smooth muscle cells (VSMC) using the classical calcium phosphate coprecipitation technique, on the incorporation of 3H-TdR in VSMC stimulated by angiotensin II (Ang II).
RESULTS(1) Compared with that of WKY, MKP-1 expression in heart and aorta were significantly decreased by 53% (P < 0.01) and 45% (P < 0.01) in SHR, respectively. While the expression of ERK-1 in heart and aorta of SHR were higher than that of WKY (P < 0.01). The ratio of ERK-1/MKP-1 in heart and aorta of SHR were significantly higher than that of WKY. (2) 3H-TdR incorporation in VSMC stimulated by Ang II (10(-7) mol/L) was increased by 207% (P < 0.01), compared with control group. In the transfected cells with wild MKP-1 gene, Ang II-induced incorporation of 3H-TdR lowered 63%, compared with untransfected cells (P < 0.05). There were no marked inhibitive role between mutant MKP-1-transfected cells and blank vector-transfected cells in response to Ang II, compared with Ang II group (P > 0.05).
CONCLUSIONThese results showed that the expression of ERK-1 in heart and aorta isolated from SHR, which stimulated proliferation and hypertrophy of cells, is higher than that of MKP-1 which dephosphorylates and inactivated ERK-1. In addition, MKP-1 significantly inhibits Ang II-stimulated proliferation of VSMC.
