title: β-arrestin is critical for early shear stress-induced Akt/eNOS activation in human vascular endothelial cells.
abstract: Recent evidence suggests that β-arrestins, which are involved in G protein-coupled receptors desensitization, may influence mechanotransduction. Here, we observed that nitric oxide (NO) production was abrogated in human saphenous vein endothelial cells (SVECs) transfected with siRNA against β-arrestin 1 and 2 subjected to shear stress (SS, 15 dynes/cm2, 10 min). The downregulation of β-arrestins 1/2 in SVECs cells also prevented the SS-induced rise in levels of phosphorylation of Akt and endothelial nitric oxide synthase (eNOS, Serine 1177). Interestingly, immunoprecipitation revealed that β-arrestin interacts with Akt, eNOS and caveolin-1 and these interactions are not influenced by SS. Our data indicate that β-arrestins and Akt/eNOS downstream signaling are required for early SS-induced NO production in SVECs, which is consistent with the idea that β-arrestins and caveolin-1 are part of a pre-assembled complex associated with the cellular mechanotransduction machinery.
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Carneiro
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Miriam Helena
authors.initials: MH
authors.lastname: Fonseca-Alaniz
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Luís Alberto Oliveira
authors.initials: LAO
authors.lastname: Dallan
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
authors.forename: Ayumi Aurea
authors.initials: AA
authors.lastname: Miyakawa
authors.affiliation: Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil. Electronic address: krieger@incor.usp.br.
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
mesh_terms: D051242:Caveolin 1 / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013314:Stress, Mechanical; D000071559:beta-Arrestin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071560:beta-Arrestin 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000605253:ARRB1 protein, human; C000605254:ARRB2 protein, human; C495540:CAV1 protein, human; D051242:Caveolin 1; D034741:RNA, Small Interfering; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt
keywords: Endothelial cells; Mechanotransduction; Nitric oxide; Shear stress; β-arrestin