CADMIUM CHELATION THERAPY:DEV NEW AGENTS TO PREVENT/TREAT HEAVY METAL POISONING

镉螯合疗法：开发预防/治疗重金属中毒的新药物

• 批准号: 7609922
• 负责人: PETER R CRAIG
• 金额: $ 3.28万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609922
• 关键词: Affect; Affinity; Aminolevulinate; Aminolevulinic Acid; Antioxidants; Apoptosis; Binding; Binding Proteins; Cadmium; Calcium; Cells; Chelation Therapy; Computer Retrieval of Information on Scientific Projects Database; DNA; Development; Enzymes; Equilibrium; Funding; Grant; Heavy Metals; Institution; Lipids; Malignant Neoplasms; Metabolic; Metals; Molecular; New Agents; Oxidants; Oxidation-Reduction; Oxidoreductase; Physical condensation; Porphobilinogen; Potassium; Proteins; Reporting; Research; Research Personnel; Resources; Source; Testing; United States National Institutes of Health; Water; cytotoxicity; heme a; magnesium ion; metal poisoning; oxidation; prevent; protein expression; response; therapy development

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cadmium chelation therapy: Development of new agents to prevent or treat heavy metal poisoning Cellular responses to cadmium include metabolic changes, sequestering by metal binding proteins and programmed cell death or apoptosis. The effects of the presence of cadmium at the molecular level have been less well documented. One report described how cadmium inhibited delta-aminolevulinate dehydrogenase, an enzyme that catalyzes the condensation of two delta-aminolevulinic acid molecules to yield porphobilinogen (a heme precursor), leading to disrupted development. Another study described how such heavy metals induce oxidative damage leading to cancer. These authors found that the presence of non-redox active heavy metals (Cd, Pb, Hg and As) with an affinity for cellular antioxidants disrupted the antioxidant/oxidant balance such that adverse oxidation occurred to cellular components such lipids, proteins and DNA. We propose to synthesize, characterize and test the cadmium-sequestering selectivity and efficiency of the hydrophilic xanthates, dithiocarbamates and thioketones. The following hypotheses will be tested during the course of the project: 1) To determine that potassium dithiocarbamates, potassium xanthates and thioketones are water soluble; 2) To determine whether these molecules will bind cadmium efficiently and selectively in the presence of calcium and magnesium ions; 3) To determine the level of cytotoxicity of candidate cadmium-sequestering agents; and 4) To determine whether the candidate sequestering molecules affect protein expression in cells.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 镉螯合疗法：预防或治疗重金属中毒的新药开发 细胞对镉的反应包括代谢变化、金属结合蛋白的螯合和程序性细胞死亡或凋亡。镉在分子水平上的影响还没有得到很好的证明。一份报告描述了镉如何抑制δ-氨基酮戊酸脱氢酶（一种催化两个δ-氨基酮戊酸分子缩合产生胆色素原（一种血红素前体）的酶），从而导致发育中断。另一项研究描述了这些重金属如何诱导氧化损伤导致癌症。这些作者发现，非氧化还原活性重金属（镉，铅，汞和砷）的存在与细胞抗氧化剂的亲和力破坏了抗氧化剂/氧化剂的平衡，使细胞成分，如脂质，蛋白质和DNA发生不利的氧化。 我们拟合成、表征和测试亲水性黄原酸酯、二硫代氨基甲酸酯和硫酮的镉螯合选择性和效率。在项目过程中将检验以下假设：1）确定二硫代氨基甲酸钾、黄原酸钾和硫酮是水溶性的; 2）确定这些分子在钙和镁离子存在下是否有效和选择性地结合镉; 3）确定候选镉螯合剂的细胞毒性水平;和4）确定候选螯合分子是否影响细胞中的蛋白质表达。