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High Blood PressureResearch 2010Scientific SessionsAbstracts 2010 год

High Blood Pressure Research 2010 Scientific Sessions Abstracts
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: c-Src activation/translocation to cholesterol-enriched microdomains is a novel non-genomic signaling pathway for aldosterone in vascular smooth muscle cells (VSMCs).Caveolae have been identified as enriched sites of platelet-derived growth factor receptor (PDGFR), which stimulate the recruitment of multiple signaling molecules to lipid rafts including c-Src.In this study we questioned whether PDGFR mediates aldosterone-induced c-Src translocation to cholesterol-enriched domain /caveolae and the associated inflammatory effects.In vitro studies were performed in cultured VSMCs from WKY rats.Cholesterol-enriched fractions were obtained by sucrose-gradient centrifugation.VSMC inflammatory responses were evaluated by adhesion molecule expression and monocyte adhesion assay.In VSMCs, aldosterone-induced phosphorylation of PDGFR (280Ϯ15%), c-Src (168Ϯ5%) and its downstream target Pyk2 (350Ϯ30%) was inhibited by PDGFR inhibitor, AG1296, and cholesterol depletion with methyl-a ˆ-clyclodextrin.Cholesterol replacement recovered aldosterone effects.Aldosterone stimulation increased c-Src phosphorylation and trafficking into lipid rafts/caveolae without affecting PDGFR content in these microdomains.AG1296 prevented c-Src translocation.PDGFR is highly phosphorylated by aldosterone in cholesterol-enriched fractions (2-fold).Aldosterone stimulated vascular expression of ICAM-1 (180Ϯ22 %) and VCAM-1 (210Ϯ25 %) and promoted monocyte adhesion to VSMCs, responses that were inhibited by cholesterol depletion or caveolin-1 deficiency.AG1296 and PP2, c-Src inhibitor, blocked these effects.Mineralocorticoid receptors (MR) were localized in caveolin-1 and flotillin-2-rich fractions and co-immunoprecipitated with caveolin-1, PDGFR and c-SRC indicating MR/signalling lipid raft association.We demonstrate that aldosterone-mediated c-Src trafficking/activation and pro-inflammatory signaling involve lipid rafts/caveolae and PDGFR.These findings identify cholesterol-rich microdomains as dynamic scaffolding systems for non-genomic signaling by aldosterone/MR/PDGFR.
Год издания: 2010
Издательство: Lippincott Williams & Wilkins
Источник: Hypertension
Ключевые слова: Hormonal Regulation and Hypertension, Blood Pressure and Hypertension Studies