抄録
BACKGROUND: The herbal medicine Sairei-to is efficacious in renal diseases where mesangial proliferation is a key event. We examined whether Sairei-to inhibits proliferation of cultured rat mesangial cells and investigated its mechanism of action. METHODS: The effect of Sairei-to on [(3)H]-thymidine incorporation stimulated by serum was assessed. Cell cycle was analyzed by flowcytometry. Extracellular signal-regulated kinase (ERK) activity was determined by immunecomplex kinase assay. Tyrosine phosphorylation of cellular proteins, and phosphorylation of ERK and Raf-1 were analyzed by immunoblot. Cyclic AMP was measured by radioimmunoassay. RESULTS: Incubation of mesangial cells for 18 h with water-soluble but not insoluble fraction of Sairei-to inhibited serum-stimulated [(3)H]-thymidine incorporation. In subsequent experiments, water-soluble fraction, at a dose required for a half-maximal response (2 mg/ml), was used. Sairei-to inhibited S-phase entry stimulated by serum. Serum-induced tyrosine phosphorylation of p44 and p42 ERK was inhibited by Sairei-to, but that of other cellular proteins was not affected. Suppression of serum-stimulated ERK activation by Sairei-to was confirmed by immunecomplex kinase assay. Activation of Raf-1, an upstream activator of ERK, was also attenuated by Sairei-to. Incubation of cells with Sairei-to significantly increased the generation of cAMP. CONCLUSIONS: Sairei-to inhibits serum-induced DNA synthesis of rat mesangial cells by suppressing Raf-1/ERK cascade probably via cAMP.
本文言語 | English |
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ページ(範囲) | 652-659 |
ページ数 | 8 |
ジャーナル | Nephron |
巻 | 92 |
号 | 3 |
DOI | |
出版ステータス | Published - 2002 |
ASJC Scopus subject areas
- 生理学
- 腎臓病学
- 生理学(医学)
- 泌尿器学