课题基金 / 基金详情

IRON AND TOXICITES AND PATHOLOGIES

IRON AND TOXICITES AND PATHOLOGIES
铁与毒性和病理学
批准号:
2153931
负责人:
STEVEN D. AUST
金额:
$17.36万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-05-01 至 1998-08-31

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中文摘要
翻译
这是我们继续研究铁在各种疾病中的作用的建议
英文摘要
This is a proposal to continue our research on the role of iron in various toxicities and pathologies. Iron is very reactive, able to oxidize biomolecules directly or indirectly by the generation of the hydroxyl radical (OH) by Fenton reaction (Fe + H202 yielding Fe111 + 0H + OH-). Iron can be released from the iron storage protein ferritin by the free radical form of various toxins, generated by NADPH-cytochrome reductase, and superoxide, which can result from toxins that redox cycle. Free radicals can also be produced by the one-electron oxidation of chemicals by peroxidases. We propose that these enzymes (peroxidases) and various other chemicals can also release iron from ferritin. We have recently discovered that 02 is also produced by the oxidation of H202 by various radicals produced by peroxidases. We therefore propose to investigate the release of iron from ferritin by peroxidases and toxins that are known to be substrates for peroxidases (i.e., hydroquinones, chlorpromazine, phenytoin, di- and trimethadione, aminotriazole, tetramethylbenzidine, etc.). We will also investigate the role of O2 in the release of iron from ferritin by these chemicals and enzymes. On the other hand, ferritin may be protective against the toxic effects of iron if there is an efficient mechanism for placing the iron into ferritin. We don't believe that ferritin has its own iron loading ability. We propose that this is the role of ceruloplasmin. However, we must show that ceruloplasmin is a tissue enzyme and that it associates with ferritin to efficiently load iron into the ferritin. We will also demonstrate that ceruloplasmin and ferritin are protective against iron-catalyzed lipid peroxidation by the release mechanisms noted above, especially in the presence of various biomolecules that can complex with iron. We also propose to determine if several proposed antioxidants that may chelate iron can inhibit peroxidase and ferritin-dependent lipid peroxidation.
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IRON LOADING INTO FERRITIN
  • 批准号:
    2906053
  • 项目类别:
  • 资助金额:
    $16.73万
  • 财政年份:
    1997
  • 负责人:
    STEVEN D. AUST
  • 依托单位:
IRON LOADING INTO FERRITIN
  • 批准号:
    2749626
  • 项目类别:
  • 资助金额:
    $16.24万
  • 财政年份:
    1997
  • 负责人:
    STEVEN D. AUST
  • 依托单位:
IRON LOADING INTO FERRITIN
  • 批准号:
    2372437
  • 项目类别:
  • 资助金额:
    $15.77万
  • 财政年份:
    1997
  • 负责人:
    STEVEN D. AUST
  • 依托单位:
ROLE OF IRON IN TOXICITIES AND PATHOLOGIES
  • 批准号:
    3253295
  • 项目类别:
  • 资助金额:
    $9.27万
  • 财政年份:
    1989
  • 负责人:
    STEVEN D. AUST
  • 依托单位:
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