Project/Area Number |
08408028
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Functional biochemistry
|
Research Institution | Osaka University |
Principal Investigator |
TANIGUCHI Naoyuki Osaka University Medical School, Professor, 医学部, 教授 (90002188)
|
Co-Investigator(Kenkyū-buntansha) |
CHUNG Mun Ok Osaka University Medical School, Assistant Professor, 医学部, 助手 (60252657)
HIGASHIYAMA Shigeki Osaka University Medical School, Assistant Professor, 医学部, 助手 (60202272)
SUZUKI Keiichiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (70221322)
FUJII Junichi Osaka University Medical School, Associate Professor, 医学部, 助教授 (00222258)
|
Project Period (FY) |
1996 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥33,100,000 (Direct Cost: ¥33,100,000)
Fiscal Year 1997: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1996: ¥27,000,000 (Direct Cost: ¥27,000,000)
|
Keywords | Reactive oxygen species / Antioxidants / Apoptosis / Diabetic complications / Glycation / Growth factor / 3-Deoxyglucosone / Signal transduction / 活性酸素 / 一酸化窒素 / 形質転換増殖因子 / ヘパリン結合性上皮増殖因子 / 2-オキソアルデヒド化合物 / スーパーオキシドディスムターゼ / グルタチオンペルオキシダーゼ |
Research Abstract |
We have investigated the glycation reaction which is assumed to be involved in aging and diabetes mellitus. Especially, effects of its early reaction products on antioxidative enzymes were examined. As results, cells exposed to reducing sugars such as fructose underwent apoptosis. On the other hand, 3-deoxyglucosone and methylglyoxal, reaction intermediates of the glycation reaction and very toxic compounds, were found to induce apoptosis in certain cells. An antibody was raised against fructated intermediary product of proteins with fructose (fructated lysine). We confirmed that crystallins were fructated in rat lens where the polyol metabolic pathway is active. In addition, we examined relationship between mechanism of induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) by glycation intermediates and growth of smooth muscle cells. Methylglyoxal and 3-deoxyglucosone induced HB-EGF expression in smooth muscle cells. While these intermediate increased the intracellular peroxides, N-acetylcysteine, an antioxidant, rather suppressed the gene expression. These data suggest that reactive oxygen species are somehow involved in the expression of HB-EGF gene.
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