AIM AND METHODS: To 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). CONCLUSION: These 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.
Angiotensin II/pharmacology , Aorta/enzymology , Dual Specificity Phosphatase 1/metabolism , Myocardium/enzymology , Myocytes, Smooth Muscle/metabolism , Animals , Aorta/cytology , Cell Proliferation , Cells, Cultured , Heart , Hypertension/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Muscle, Smooth, Vascular/cytology , Myocardium/cytology , Myocytes, Smooth Muscle/drug effects , Rats , Rats, Inbred SHR , Rats, Inbred WKY
Changes of activity and content of myocardial group II phospholipase A(2) and its mRNA transcription and stability during rat sepsis were investigated. Results showed that, compared with control group,myocardial group II phospholipase A(2) activity in early and late sepsis decreased by 25.0%(P<0.05) and increased by 47.6%(P<0.01),respectively group II phospholipase A(2) protein concentration reduced by 27.0% and augmented by 48.0%(P<0.01),respectively. Myocardial group II phospholipase A(2) mRNA transcription rate and content showed similar two-phases changes. The mRNA transcription rate during early and late sepsis decreased by 45.0% and increased by 70.0%(P<0.01),respectively. The mRNA content decreased by 34.1% in early sepsis and increased by 157.0% in late sepsis(P<0.01), respectively. The half-life of group II phospholipase A(2) mRNA remained unchanged notably during early and late stage of sepsis. These data suggest that myocardial group II phospholipase A(2) activity decreased in early stage of sepsis and increased in its late stage, and these changes were regulated transcriptionally.
