title: Enhanced expression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats via MAP kinase- and PI3 kinase-independent pathways.
abstract: Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit hyperproliferation, enhanced MAP kinase (MAPK) activity, and overexpression of Giα proteins. This study was undertaken to examine whether the overexpression of Giα proteins contributes to the hyperproliferation of VSMC of SHR through MAPK signaling. The hyperproliferation of VSMC from SHR in the absence and presence of angiotensin II was restored towards those in Wistar-Kyoto (WKY) rats levels by pertussis toxin (PT) treatment. In addition, siRNA knockdown of Giα proteins also resulted in the attenuation of hyperproliferation towards control levels. The overexpression of Giα proteins was also inhibited by MAPK and PI3 kinase (PI3K) inhibitors. In addition, the hyperproliferation and enhanced phosphorylation of ERK1/2 and Akt in VSMC from SHR were attenuated towards WKY levels by the inhibitors of MAPK, PI3K, c-Src, and antioxidants, whereas PT was unable to attenuate the enhanced phosphorylation of ERK1/2 and Akt. Furthermore, 8Br-cAMP and forskolin also attenuated the hyperproliferation of VSMC from SHR. These results suggest that the hyperproliferation of VSMC from SHR may be attributed to the enhanced expression of Giα proteins and increased activation of MAPK and PI3 kinase. However, Giα-mediated hyperproliferation may not be mediated through MAPK- and PI3 kinase-dependent pathways and may involve decreased levels of intracellular cAMP.
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada.|Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Grace
authors.initials: G
authors.lastname: Bou Daou
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada.|Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada.|Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Madhu B
authors.initials: MB
authors.lastname: Anand-Srivastava
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction
chemical_list: D004247:DNA; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D051057:Proto-Oncogene Proteins c-akt; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: Gi proteins; MAP kinase/PI3 kinase; SHR; VSMC proliferation; oxidative stress; prolifération des CMLV; protéines Gi; rat SHR; stress oxydatif