|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|2192726||1097975||2017||14 صفحه PDF||ندارد||دانلود کنید|
The in vivo signal transduction pathway, responsible for isoproterenol-induced cardiac hypertrophy or remodeling, remains to be clarified. The purpose of this study was to examine c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), activator protein-1 (AP-1) and nuclear factor-κB (NK-κB) DNA binding activity, which seem to be important in a signal transduction cascade upstream of the increased level of mRNA expression observed in isoproterenol-induced cardiac remodeling. Rats were continuously infused with saline and isoproterenol by intravenous injection (a short period; 0.5μg/kg/min) and an osmotic minipump (a long period; 0.5 or 3 mg/kg/day). Cardiac morphology was measured by echocardiography. JNK and ERK were measured by in gel kinase assay. AP-1 and NF-κB DNA binding activity was determined using an electrophoretic mobility shift assay. Echocardiogram showed that the thickness of the left ventricular anterior wall (AW) and left ventricular posterior wall (PW) increased at day 1 in low doses, and at day 1 in high doses. Isoproterenol significantly increased ERK and JNK activity at 15 min after intravenous infusion of 0.5μg/kg/min isoproterenol. At late phase about JNK and ERK activity, only a high dose of isoproterenol increased JNK. AP-1 DNA binding activities spurred by low or high doses of isoproterenol administration increased at 12 h, reached their peak of 24.1- and 37.1-fold (P<0.01), respectively, at 24 h, and thereafter decreased. Although low doses of isoproterenol did not change the level of NF-κB DNA binding activities, high doses increased it to 10.9-fold (P<0.01) at day 2. This study showed increased JNK, ERK, AP-1 and NF-κB DNA binding activities in isoproterenol-induced cardiac remodeling. AP-1 may contribute to the isoproterenol-induced cardiac remodeling, and JNK or NF-κB may also play some roles in it.
Journal: Journal of Molecular and Cellular Cardiology - Volume 31, Issue 11, November 1999, Pages 2017–2030