| Project/Area Number |
10044286
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
TANIGUCHI Naoyuki Osaka University, Graduate School of medicine, Professor, 医学系研究科, 教授 (90002188)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Junichi Yamagata University, School of Medicine, Professor, 医学部, 教授 (00222258)
SUZUKI Keiichiro Hyogo College of Medicine, Professor, 教授 (70221322)
HIGASHIYAMA Shigeki Osaka University, School of Allied Health Sciences, Associate Professor, 医学部, 助教授 (60202272)
IKEDA Yoshitaka Osaka University, Graduate School of medicine, Assistant Professor, 医学系研究科, 助手 (60252657)
TAKAHASHI Motoko Osaka University, Graduate School of medicine, Assistant Professor, 医学系研究科, 助手 (00303941)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 2000: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1999: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Reactive oxygen species / glutathine / nitric oxide / redox balance / growth factor / glutathione peroxidase / NO合成酵素 / ペルオキシレドキシン |
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| Research Abstract |
Reactive oxygen species(ROS) such as the superoxide anion (O_2^-), hydrogen peroxide (H_2O_2) and the hydroxyl radical (OH) are represent putative biohazards when present in excess, a condition which,is referred to as "oxidative stress". ROS are generated within cells as byproducts of biological oxidations and are thought to play important roles in several pathophysiologic events, including inflammation, mutagenesis, and aging. Recently ROS and redox balance are thought to act as an intracellular signal and have a wide variety of biological action. So in this project we have demonstrated new biological functions of ROS, glutathione and redox balance.
1)Inactivation of glutathine peroxidase by reducing sugars and dicarbonyl compounds
2)New biological faction of peroxiredixin family : Purification and cloning of peroxiredoxin IV and its antioxidative property in extracellular space
3)Ceruloplasmin(Cp) has a glutathione peroxidase-like activity together with its ferroxidase activity and would completely remove the primary reactants required for both Fenton chemistry and lipid peroxidation. And Cp binds to extracellular myeloperoxidase(MPO) and prevents MPO making HOC1, a powerful oxidant which will lead to molecular damage.
4)Hydroxyl radicals accelerates the adhesion of neutrophils and cancer cells to endothelial cells in the absence of de novo protein synthesis
5)Mechanisms of anti-oxidative functions of glutathione, giutathione peroxidase and γ GCS, especially involvement of signal transduction.
6)Nitric oxide inactivates glutathione peroxidase and the accumulated hydrogen peroxide induces Heparin-binding EGF-like growth factor(HB-EGF) as an autocrine protective factor in rat aortic smooth muscle cells via the JNK pathway.
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