|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
(1) Elevation of Glutathione Level in Rat Hepatocytes by Hepatocyte Growth Factor via Induction of γ-Glutamylcysteine Synthetase : Hepatocyte growth factor (HGF) was found to cause a dose-and time-dependent increase in intracellular glutathione (GSH) level in rat hepatocytes. The activity of γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme of GSH biosynthesis, was also increased by HGF. Northern blot analysis revealed the induction of γ-GCS mRNA. These results suggested that the induction of GSH synthesis by HGH is associated with the transcriptional activation of γ-GCS gene and the subsequent elevation of γ-GCS activity.
(2) Expression of γ-Glutamylcysteine Synthetase mRNA in Regenerating Rat Liver : The GSH level γ-GCS activity increased in regenerating rat liver, reaching a maximum on day 2. Furthermore, γ-GCS mRNA expression increased within 24 h and reached maximum on day 2. These results suggest that the increased GSH level in regenerating rat liver after partial he
patectomy is associated with the transcriptional activation of γ-GCS gene and the sequence elevation in γ-GCS activity.
(3) Saccharomyces cerevisiae cultured under aerobic and anaerobic conditions : air-level oxygen stress and protection against stress : Cells of Saccharomyces cerevisiae were grown aerobically and anaerobically, and levels of the protective compounds, cysteine and glutathione, and activities of defensive enzynes, catalase and superoxide dismutase, against an oxygen stress were determined and compared in both cells. Aerobiosis increased both the compounds and enzyme activities. The elevated synthesis of glutathione could be associated with the increased levels of cysteine which in its turn was found to be controlled by the oxygen-dependent activation of cystathionine β-synthase.
部分肝切除後の肝再生時に,肝臓中グルタチオン量及びγ-GCS活性が上昇した。ノーザンブロット解析の結果,γ-GCS mRNAの発現の上昇がみられた。これらの結果より,肝再生時におけるグルタチオンの上昇はγ-GCS geneの活性化によるものであることを明らかにした(Biol.Pharm.Bull.,22(10),1113-1115(1999))。
Yeastを好気的に培養した場合,嫌気的な場合に比べてcatalaseやsuperoxide dismutaseのような活性酸素に対する防御的な酵素の活性が上昇し,また,システイン及びグルタチオン量が上昇した。このシステイン量の上昇はシステイン合成酵素であるcystathionine β-synthetaseの活性化によるものであった(Biochem.Biophys.Acta,1472,587-594(1999))。 Less