title: Role of PKCδ in Enhanced Expression of Gqα/PLCβ1 Proteins and VSMC Hypertrophy in Spontaneously Hypertensive Rats.
abstract: Gqα signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqα and PKCδ activation. We recently showed the role of enhanced expression of Gqα/PLCβ1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCδ in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCδ and the associated signaling mechanisms in VSMC hypertrophy using 16-week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKCδ-Tyr311 and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCδ. In addition, knocking down of PKCδ by PKCδ-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P)H oxidase activity, increased expression of Gqα, phospholipase C (PLC)β1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKCδ-Tyr311, IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCδ and that PKCδ is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqα and PLCβ1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling.
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Mohammed Emehdi
authors.initials: ME
authors.lastname: Atef
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Madhu B
authors.initials: MB
authors.lastname: Anand-Srivastava
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D006984:Hypertrophy; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D034622:RNA Interference; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017978:Receptors, Growth Factor / Q000378:metabolism; D013045:Species Specificity; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D017978:Receptors, Growth Factor; D013481:Superoxides; D014443:Tyrosine; C085746:rottlerin; D019255:NADPH Oxidases; D016392:Proto-Oncogene Proteins pp60(c-src); D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11