کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10954374 1097900 2005 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of c-Jun NH2-terminal kinase in G-protein-coupled receptor agonist-induced cardiac plasminogen activator inhibitor-1 expression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Role of c-Jun NH2-terminal kinase in G-protein-coupled receptor agonist-induced cardiac plasminogen activator inhibitor-1 expression
چکیده انگلیسی
Plasminogen activator inhibitor-1 (PAI-1) has been implicated as a contributing risk factor for cardiovascular disease. However, little is known about molecular mechanisms of cardiac PAI-1 gene expression. To elucidate these mechanisms, dominant negative mutants of c-Jun NH2-terminal kinase (JNK), p38MAPK, apoptosis signal-regulating kinase-1 (ASK-1) and c-Jun were overexpressed in rat neonatal ventricular cardiac myocytes and fibroblasts by adenovirus vector to abrogate the activation of the corresponding endogenous proteins. One hundred nmol/l of angiotensin II significantly enhanced the JNK and p38MAPK activities of cardiomyocytes (2.3-fold and 1.9-fold, P < 0.05) and fibroblasts (3.2-fold and 2.5-fold, P < 0.05). At 3 h after stimulation, angiotensin II was found to have significantly increased PAI-1 mRNA, by 5.2-fold in cardiomyocytes and by 9.7-fold in fibroblasts. Dominant negative mutants of JNK, ASK-1 and c-Jun significantly inhibited PAI-1 mRNA expression and protein synthesis in both cardiomyocytes and fibroblasts, whereas a dominant negative mutant of p38MAPK did not change this expression. Moreover, a dominant negative mutant of JNK also significantly prevented the induction of PAI-1 mRNA expression by 100 nmol/l endothelin-1 and 10 μmol/l phenylephrine. In conclusion, G-protein-coupled receptor agonist-induced PAI-1 expression is partially mediated through JNK activation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 38, Issue 4, April 2005, Pages 583-592
نویسندگان
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