| Project/Area Number |
09670163
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | AICHI MEDICAL UNIVERSITY |
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Principal Investigator |
YOSHINO Masataka AICHI MEDICAL UNIVERSITY,SCHOOL OF MEDICINE,PROFESSOR, 医学部, 教授 (70046077)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Keiko AICHI MEDICAL UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT, 医学部, 助手 (10139652)
TSUBOUCHI Ryoko AICHI MEDICAL UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT, 医学部, 助手 (30140049)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | ALUMINUM / REACTIVE OXYGEN SPECIES / HYDROXYL RADICAL / NADP-ISOCITRATE DEHYDROGENASE / TRANSITION METALS / PC12 CELLS / APOPTOSIS / 還移金属 |
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| Research Abstract |
1. Stimulation by aluminum ion of iron-mediated lipid peroxidation
Aluminum ion enhanced the iron-mediated lipid peroxidation as the formation of thiobarbituric acid-reactive substances. Prooxidant action of aluminum was analyzed in relation to the iron coordination. Aluminum ion inhibited the autooxidation of Fe^<2+> markedly. Aluminum acts as a prooxidant by stabilizing reduced iron the initiating species for lipid peroxidation.
2. Role of metals in the regulation of NADP-isocitrate dehydrogenase
Catalytic and regulatory properties of NADP-isocitrate dehydrogenase are closely related to the ionic radii of essential metal cations such as Mn, Mg, Cd, Co, Zn, Fe and Ni. Binding of ferrous ion the prooxidant to the active sites of the enzyme results in an enhanced disruption of antioxidant enzyme system by an inactivation of NADPisocitrate dehydrogenase the principal antioxidant enzyme.
3. Interaction of aluminum with ATP and spermine
Aluminum inhibited hexokinase and glycerol kinase competitively with respect to the substrate MgATP.Spermine prevented these enzymes from the inhibition by aluminum ion. This reversal of the inhibition can be explained by NMR spectroscopic results, which show the specific spermine-mediated elimination of aluminum from the metal-ATP complex, bur no clissociaton of MgATP complex by spermine. Effect of spermine on the metal-ATP complexes may be related to the age-dependent expression of aluminum toxicity.
4. Aluminum-induced apoptotic cell death of PC12
Aluminum-maltol complex induced the apoptosis of PC12 cells, whereas aluminum at 10 times higher concentrations did not show any toxic effect on the cells. Aluminum-induced apoptosis was associated with the elevation of reactive oxygen species in PC12 cells. Aluminum can act as a prooxidant causing apoptosis of nerve cells.
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