MODIFICATION OF REACTIVE OXYGEN SPECIES-INDUCED CELL DEATH BY THE INCREASED ZINC IN RESPONSE TO STRESS

应激反应中锌的增加对活性氧诱导的细胞死亡的影响

• 批准号: 10672110
• 负责人: SATO Masao
• 金额: $ 1.73万
• 依托单位: TOKUSHIMA-BUNRIUNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672110/
• 关键词: METALLOTHIONEIN; APOPTOSIS; ZINC; TUMOR NECROSIS FACTOR; OXIDATIVE STRESS; MITOCHONDRIA; シトコンドリア; チトクロームC

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.

锌对于细胞的存活是必不可少的，并且对于许多酶和锌指蛋白等的功能是必需的，并且已知受保护的作用免受细胞损伤。锌在响应各种应力的组织中积聚在组织中。最近，已经表明，在短暂的全球瞬间是Chemia之后，超出锌的锌可能会通过易受伤害神经元中的可螯合锌的累积为化学。另一方面，细胞内锌的耗竭会诱导神经元细胞凋亡，而锌则是抗凋亡金属。对细胞存活的受保护和有毒作用是必需的。与吡啶二酮，锌离子载体，增加锌含量，增加了细胞培养基中锌和吡啶家共存的HL-60细胞的处理，进一步增加了细胞中的锌含量，并显示了DNA片段，并显示了DNA片段，并显示了Apoptoss的Hallmarks of Apoptoss。仅在硫杆菌存在的锌的一定浓度下观察到。在较高的锌浓度下，没有观察到，而HL-60细胞的生存力显着降低，这表明细胞死亡的模式是坏死的。在fibloblast细胞中获得了相似的结果。数据表明细胞内Zn的浓度决定了锌诱导的细胞死亡模式。肿瘤坏死因子（TNF）通过氧自由基物种起作用。锌和TNF的共存加速了细胞死亡。 TNF降低了正常（金属噻硫氨酸，MT +/ +）ITO细胞的宽比降低，而MT（ - / - ）ITO细胞不影响MT（ - / - ）。数据表明，金属氨酸修饰TNF.TNF诱导的细胞死亡不会影响IKB-α，p38 MAPK等。需要进一步的研究来确定MT在TNF诱导的细胞死亡中的作用。

项目成果

Kondoh M.ら 他4名(5番目): "cytochrome C release from mitochondria induced by Cadmium"J.Health Sci.. 47. 78-82 (2001)

Kondoh M. 等人和其他 4 人（第 5 篇）：“镉诱导的线粒体中的细胞色素 C 释放”J.Health Sci.. 47. 78-82 (2001)

MASUO KONDOH, SATOKO OGASAWARA SAEKO ARARAGI, MINORU HIGASIMOTO, MASAO SATO: "CYTOCHROME C RELEASE FROM MITOCHONDORIA INDUCED BY CADMIUM"J.HEALTH SCI.. 47. 78-82 (2001)

MASUO KONDOH、SATOKO OGASAWARA SAEKO ARARAGI、MINORU HIGASIMOTO、MASAO SATO：“镉诱导的线粒体中细胞色素 C 的释放”J.HEALTH SCI.. 47. 78-82 (2001)

Kondoh M. ら他4名(5番目): "Cytochrome C release from mitochondria induced by cadmium"J.health Sci.. 47. 78-82 (2001)

Kondoh M. 和其他 4 人（第 5 次）：“镉诱导的线粒体释放细胞色素 C”J.health Sci.. 47. 78-82 (2001)