Taurine suppresses platelet-derived growth factor (PDGF) BB-induced PDGF-beta receptor phosphorylation by protein tyrosine phosphatase-mediated dephosphorylation in vascular smooth muscle cells.
Taurine suppresses platelet-derived growth factor (PDGF) BB-induced PDGF-beta receptor phosphorylation by protein tyrosine phosphatase-mediated dephosphorylation in vascular smooth muscle cells.
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DOI：
10.1016/j.bbamcr.2005.07.005
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发表时间：
2005-09
期刊：
影响因子：
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通讯作者：
H. Yoshimura;Y. Nariai;M. Terashima;Toshifumi Mitani;Y. Tanigawa
中科院分区：
文献类型：
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作者：
H. Yoshimura;Y. Nariai;M. Terashima;Toshifumi Mitani;Y. Tanigawa
在动脉粥样硬化中，血管平滑肌细胞（VSMC）的异常增殖在形成纤维增生性病变中起重要作用，而血小板衍生生长因子（PDGF）-BB是VSMC最强的趋化因子和增殖因子之一。牛磺酸是一种含硫的β-氨基酸，被认为可以预防动脉粥样硬化的发展，但其分子机制尚不清楚。以前，我们证明牛磺酸显着抑制PDGF-BB诱导的细胞增殖，DNA合成，立即早期基因表达和细胞外信号调节激酶（ERK）1/2磷酸化的VSMCs。本研究旨在阐明牛磺酸在PDGF-BB信号通路中的确切分子机制。牛磺酸可显著抑制PDGF-BB诱导的PDGF-β受体磷酸化及其下游信号分子Ras、MAPK/ERK激酶（MEK）1/2和Akt的激活。由于牛磺酸不能减弱佛波酯（PMA）诱导的PDGF-β受体非依赖性ERK 1/2磷酸化，我们进一步研究了牛磺酸在PDGF-β受体水平上的抑制机制。虽然牛磺酸在体外并不直接影响PDGF受体的自磷酸化，但牛磺酸可促进PDGF-β受体的去磷酸化，并恢复PDGF-BB诱导的蛋白酪氨酸磷酸酶（PTP 3）活性抑制。综上所述，我们认为牛磺酸可能通过抑制血管平滑肌细胞PDGF-β受体的磷酸化，降低其下游信号分子的活化，从而预防或延缓动脉粥样硬化的进展。
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.