MODIFICATION OF REACTIVE OXYGEN SPECIES-INDUCED CELL DEATH BY THE INCREASED ZINC IN RESPONSE TO STRESS
| Project/Area Number |
10672110
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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 |
Environmental pharmacy
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| Research Institution | TOKUSHIMA-BUNRIUNIVERSITY |
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Principal Investigator |
SATO Masao TOKUSHIMA-BUNRI UNIVERSITY, PROFESSOR, 薬学部, 教授 (20045743)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANUMA Akira TOHOKU UNIVERSITY, PROFESSOR, 大学院・薬学研究科, 教授 (80155952)
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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 |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | METALLOTHIONEIN / APOPTOSIS / ZINC / TUMOR NECROSIS FACTOR / OXIDATIVE STRESS / MITOCHONDRIA / シトコンドリア / チトクロームC |
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| Research Abstract |
Zinc is essential for the survival of the cells, and is required for the functions of many enzymes and zinc-finger proteins etc., and is known to be protective role against cell damage. Zinc accumulates in tissues in response to various kinds of stresses. Recently, it has been shown that excessively released zinc may selective neuronal death after transient global is chemia by accumulati on of chelatable zinc in vulnerable neurons. On the other hand, depletion of intracellular zinc induces neuronal apoptosis, and zinc is known to be anti-apoptotic metal. The studies are required for both protective and toxic actions for the survival of the cells.
Treatment of HL-60 cells with pyrithione, zinc ionophore, increased the zinc content, and co- existence of zinc and pyrithione in the cell culture medium further increased the zinc content in the cells, and showed DNA fragmentation, one of the hallmarks of apoptosis. The fragmentation was observed only at the certain concentration of zinc in the presence of pyrithione. At the higher concentration of zinc, it was not observed, whereas the viability of the HL-60 cells was significantly decreased, suggesting that mode of the cell death is necrosis. Similar results were obtained in fibloblast cells. Data indicate that the concentration of Zn within cells determines mode of zinc-induce cell death.
Tumor necrosis factor (TNF) acts via oxygen radical species. Co-existence of zinc and TNF accelerates cell death. TNF decreased viabilitv of normal (metallothionein, MT +/+) Ito cells, whereas MT(-/-) Ito cells were not affected. The data suggest that metallothionein modifies cell death-induced by TNF.TNF did not affect IkB- α, p38 MAPK etc. Further studies are required to establish the role of MT in TNF-induced cell death.
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Report
(4 results)
Research Products
(3 results)
