Premium
Eukaryotic elongation factor 2 kinase controls proliferation and migration of vascular smooth muscle cells
Author(s) -
Usui T.,
Nijima R.,
Sakatsume T.,
Otani K.,
Kameshima S.,
Okada M.,
Yamawaki H.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12354
Subject(s) - elongation , microbiology and biotechnology , elongation factor , vascular smooth muscle , smooth muscle , kinase , biology , endocrinology , biochemistry , materials science , gene , ribosome , rna , ultimate tensile strength , metallurgy
Aim Eukaryotic elongation factor 2 kinase ( eEF 2K), also known as calmodulin (CaM)‐dependent protein kinase (CaMK) III, is a unique member of CaMK family protein. We have recently found that expression of eEF 2K protein increased in mesenteric artery from spontaneously hypertensive rats. As pathogenesis of hypertension is in part regulated by vascular structural remodelling via proliferation and migration of vascular smooth muscle cells (SMCs), we tested the hypothesis that eEF 2K controls SMCs proliferation and migration. Methodsand results In rat mesenteric arterial SMCs, an eEF 2K inhibitor, A‐484954 (10 μ m ), significantly inhibited platelet‐derived growth factor (PDGF)‐BB (10 ng mL −1 )‐induced SMCs proliferation as determined by a cell counting and bromodeoxyuridine incorporation assay. PDGF‐BB (10 ng mL −1 )‐induced SMCs migration was significantly inhibited by A‐484954 (10 μ m ) as determined by a Boyden chamber assay. A‐484954 (10 μ m ) significantly inhibited PDGF‐BB (10 ng mL −1 )‐induced phosphorylation of eEF 2K, extracellular signal‐regulated kinase (ERK), Akt, p38 and heat‐shock protein (HSP) 27 as determined by Western blotting. It was confirmed that a CaM inhibitor, W‐7 (50 μ m ), inhibited PDGF‐BB (10 ng mL −1 )‐induced phosphorylation of eEF 2K. In an ex vivo mesenteric arterial ring assay, 10% foetal bovine serum‐induced SMCs outgrowth was significantly inhibited by A‐484954 (10 μ m ). Conclusion We for the first time revealed that eEF 2K mediates PDGF‐BB‐induced SMCs proliferation and migration through activating ERK, Akt, p38 and HSP27 signals in a CaM‐dependent manner. Our results suggest eEF 2K as a novel pharmaceutical target for the prevention of hypertensive cardiovascular diseases.