Project/Area Number |
13680706
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Functional biochemistry
|
Research Institution | University of Tsukuba |
Principal Investigator |
SATO Hideyo Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (60235380)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
Keywords | cystine / amino acid transport / oxidative stress / glutathione / transcriptional regulation |
Research Abstract |
Glutathione is one of the essential molecules for the antioxidant system. In mammalian cells, the cystine/glutamate exchange transporter designated system x_c^- plays an important role for maintaining the intracellular glutathione level. In this study, the regulatory mechanism of the expression of xCT consisting of system x_c^- was investigated and the following results were obtained. (1) The induction of xCT mRNA by electrophilic reagents was regulated via electrophile response element (EpRE) located on approximately 150 bp upstream of the transcription initiation site of mouse xCT gene. This induction was mediated by a transcription factor, Nrf2. (2) The induction of xCT mRNA by cystine deficiency was regulated via the region consisting of approximately 30 bp located on the downstream of EpRE. (3) The xCT mRNA was strongly expressed in circumventricular organ and meninges in the mouse brain. (4) The activity of system x_c^- was induced by co-expressing xCT and rBAT as well as by co-expressing xCT and 4F2hc in Xenopus oocytes and NIH3T3 cells.
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