Suppressive Effect of Taurine on Platelet-Derived Growth Factor (PDGF) BB-Induced c-fos and c-jun mRNA Expressions through Extracellular Signal-Regulated Kinase (ERK) in Mesenchymal Cell Lines
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概要
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Platelet-derived growth factor (PDGF) plays an important role in the pathogenic course of atherosclerosis, pulmonary fibrosis, and gloerulonephritis, 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 mitogenactivated protein kinases (MAPKs) in NIH/3T3 cells as standard mesenchymal cells. Tau-rine 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-depen-dently, 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 phos-phorylation of the PDGF-β 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-β 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.
- 財団法人 学会誌刊行センターの論文
- 2003-06-01
著者
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Imada Keisuke
Taisho Pharmaceutical Co.
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Terashima Masaharu
Department Of Biochemistry And Molecular Medicine Shimane Medical University
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Hosokawa Yu
Department Of Food And Health Sciences Jissen Women's University
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Nariai Yuko
Department Of Biochemistry And Molecular Medicine Shimane Medical University
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Kageyama Emiko
Central Research Laboratories Shimane Medical University
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Mitani Toshifumi
Department Of Biochemistry And Molecular Medicine Shimane Medical University
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Tanigawa Yoshinori
Department Of Biochemistry And Molecular Medicine Shimane Medical University
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