Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10803181 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2005 | 11 Pages |
Abstract
In atherosclerosis, abnormal vascular smooth muscle cell (VSMC) proliferation plays an important role to form fibroproliferative lesions and platelet-derived growth factor (PDGF)-BB is one of the most potent chemoattractants and proliferative factors for VSMCs. Taurine, sulfur-containing β-amino acid, has been considered to prevent the development of atherosclerosis, although the molecular mechanism remains obscure. Previously, we demonstrated that taurine significantly suppressed PDGF-BB-induced cell proliferation, DNA synthesis, immediate-early gene expressions and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in VSMCs. The present study was aimed at elucidating the precise molecular mechanism of taurine in PDGF-BB signaling pathway. We showed that taurine significantly suppressed PDGF-BB-induced phosphorylation of PDGF-β receptor and activation of its downstream signaling molecules such as Ras, MAPK/ERK kinase (MEK)1/2 and Akt. Because taurine did not attenuate phorbol 12-myristate 13-acetate (PMA)-induced PDGF-β receptor-independent ERK1/2 phosphorylation, we further investigated the suppressive mechanism of taurine in PDGF-β receptor level. Although taurine did not directly affect PDGF receptor autophosphorylation in vitro, taurine promoted PDGF-β receptor dephosphorylation and restored PDGF-BB-induced suppression of protein tyrosine phosphatase (PTPase) activity. Taken together, we propose that taurine could prevent or delay the progression of atherosclerosis by PTPase-mediated suppression of PDGF-β receptor phosphorylation, and by decreasing the activation of its downstream signaling molecules in VSMCs.
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Authors
Hitoshi Yoshimura, Yuko Nariai, Masaharu Terashima, Toshifumi Mitani, Yoshinori Tanigawa,