title: Site specific differential activation of ras/raf/ERK signaling in rabbit isoproterenol-induced left ventricular hypertrophy.
abstract: To understand better the mediating role of ras/raf/ERK signaling pathway in development of cardiac hypertrophy and cerebrovascular events in vivo, the molecular mechanism of the pathway in heart and cerebral arteries after isoproterenol (ISO) induced beta-adrenergic receptor (betaAR) stimulation was examined in rabbit as animal model. Compared with the heart, our findings indicate that ISO-stimulation results in increase in mRNA levels of ras, raf, and immediate-early genes in the cerebral arteries. Conversely, the ras and raf protein expression levels (determined by Western blot) and the ras-GTP level (determined by pull-down assay) in the heart, but not the cerebral arteries, are markedly elevated after treatment. In addition, despite constant ERK1/2 abundance, phosphorylated ERK (pERK) activity was elevated at both sites with prominent effect on heart following stimulation. Opposing to the PKA and PKC, as upstream contributors in the pathway, which seem to be similarly affected at both sites following ISO-stimulation, the results imply that the downstream candidates ras and raf, as well as immediate-early genes, have different responses at both sites post-stimulation. The results provide an evidence of site-dependent differential response of ras/raf/ERK pathway after cardiac hypertrophy-induced by ISO-stimulation. This varied response may account for underlying mechanisms of development of cardiac hypertrophy and cerebrovascular events in heart and cerebral arteries, respectively.
authors.affiliation: Department of Physiology and Biophysics, Mitochondrial Signaling Laboratory, Mitochondria Research Group, College of Medicine, Cardiovascular and Metabolic Diseases Center, Inje University, 633-165 Gaegeum-Dong, Busanjin-Gu, Busan 614-735, Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Hyunju
authors.initials: H
authors.lastname: Kim
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Mohamad
authors.initials: M
authors.lastname: Warda
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Ko
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000318:Adrenergic beta-Agonists; D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000378:metabolism*; D007545:Isoproterenol; D020935:MAP Kinase Signaling System; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D011817:Rabbits; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D019908:Proto-Oncogene Proteins c-raf; D017868:Cyclic AMP-Dependent Protein Kinases; D051571:Protein Kinase C-alpha; D048052:Mitogen-Activated Protein Kinase 3; D018631:ras Proteins; D007545:Isoproterenol