Terashima Masaharu, Mitani Toshifumi, Hosokawa Yu, Nariai Yuko, Imada Keisuke, Kageyama Emiko, Tanigawa Yoshinori
Department of Biochemistry and Molecular Medicine, Shimane Medical University, Izumo 693-8501, Japan.
J Nutr Sci Vitaminol (Tokyo). 2003 Jun;49(3):187-94. doi: 10.3177/jnsv.49.187.
Platelet-derived growth factor (PDGF) plays an important role in the pathogenic course of atherosclerosis, pulmonary fibrosis, and glomerulonephritis, and increased activity of the PDGF signaling pathway has been implicated as a contributing factor in the progression of the diseases. Taurine may be a prophylactic amino acid for atherosclerosis not only by decreasing plasma cholesterol level, but also by inhibiting the cell proliferation-signaling pathway. To elucidate how taurine affects the signaling pathway, we investigated the effect of taurine on the expression of immediate-early genes and activation of mitogen-activated protein kinases (MAPKs) in NIH/3T3 cells as standard mesenchymal cells. Taurine inhibited PDGF-BB-induced c-fos and c-jun mRNA expressions dose-dependently, although structural analogues of taurine did not. Taurine decreased the PDGF-induced p44/p42 ERK (extracellular signal-regulated kinase) phosphorylation state dose-dependently, although no phosphorylation was observed on JNK/SAPK (c-Jun N-terminal kinase/stress-activated protein kinase) and p38 MAPK. Further, PDGF-BB-induced tyrosine phosphorylation of the PDGF-beta receptor was not influenced by treatment with taurine, indicating that taurine never affects ligand-receptor interaction, and may act downstream of the PDGF receptor. Thus, the inhibitory mechanism of taurine on PDGF-induced c-fos and c-jun mRNA expressions may depend on the p44/p42 ERK pathway, but not on PDGF-beta receptor tyrosine phosphorylation, JNK/SAPK or p38 MAPK pathway. These results suggest that taurine may suppress the cell proliferation-signaling pathway through the inhibition of ERK activity and immediate-early gene expression.
血小板衍生生长因子（PDGF）在动脉粥样硬化、肺纤维化和肾小球肾炎的发病过程中起重要作用，PDGF信号通路活性增加被认为是这些疾病进展的一个促成因素。牛磺酸可能是一种预防动脉粥样硬化的氨基酸，不仅通过降低血浆胆固醇水平，还通过抑制细胞增殖信号通路。为了阐明牛磺酸如何影响信号通路，我们研究了牛磺酸对作为标准间充质细胞的NIH/3T3细胞中早期即刻基因表达和丝裂原活化蛋白激酶（MAPKs）激活的影响。牛磺酸剂量依赖性地抑制PDGF-BB诱导的c-fos和c-jun mRNA表达，而牛磺酸的结构类似物则没有。牛磺酸剂量依赖性地降低了PDGF诱导的p44/p42 ERK（细胞外信号调节激酶）磷酸化状态，尽管在JNK/SAPK（c-Jun氨基末端激酶/应激激活蛋白激酶）和p38 MAPK上未观察到磷酸化。此外，PDGF-BB诱导的PDGF-β受体酪氨酸磷酸化不受牛磺酸处理的影响，表明牛磺酸从不影响配体-受体相互作用，可能在PDGF受体的下游起作用。因此，牛磺酸对PDGF诱导的c-fos和c-jun mRNA表达的抑制机制可能取决于p44/p42 ERK途径，而不取决于PDGF-β受体酪氨酸磷酸化、JNK/SAPK或p38 MAPK途径。这些结果表明，牛磺酸可能通过抑制ERK活性和早期即刻基因表达来抑制细胞增殖信号通路。
