FUNCTIONAL STUDIES OF CYTOSOLIC ANTIOXIDANT PROTEINS

胞质抗氧化蛋白的功能研究

• 批准号: 6336111
• 负责人: JOAN Selverstone VALENTINE
• 金额: $ 3.78万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6336111
• 关键词: Saccharomyces cerevisiae; aging; antioxidants; calcium ion; catalase; cell death; copper; cytochrome c peroxidase; cytoplasm; hydrogen peroxide; manganese; mitochondria; nutrition related tag; protein structure function; superoxide dismutase; superoxides; zinc

DESCRIPTION: Life in air is possible because uncatalyzed reactions of dioxygen in living organisms are usually slow. In addition, oxidative damage to components of healthy cells is frequently prevented or repaired by antioxidant, replacement, or repair systems that exist in the cells for the purpose of maintaining and restoring redox balance. Our approach is to study the roles of superoxide, hydrogen peroxide, metal ions, and small molecule antioxidants in the yeast S. cerevisiae. The yeast S. cerevisiae is a simple eucaryote for which extensive genetics and molecular biology exist. Many genes from higher organism have been shown to substitute functionally for their yeast analogs, and more are expected now the entire yeast genome has been sequenced and is available. When grown on a non-fermentable carbon source, yeast cells metabolize dioxygen in a fashion similar to human cells, and the cellular systems for prevention, repair, and replacement of oxidatively damaged cell components are also similar. Yeast is thus an excellent system in which to study how redox balance is maintained in healthy eucaryotic cells. These studies are expected to lead to a better understanding of redox balance in eucaryotic organisms and the role of "oxidative stress" in processes leading to human aging, cell death, and disease. We will determine the major natural sources of superoxide and hydrogen peroxide in yeast and measure their concentrations and those of small molecule antioxidants (reduced and oxidized) within the cells. These methods will be applied to the wild type strains and to a variety of mutant strains in which antioxidant systems and/or dioxygen metabolism have been modified; the results will be used to interpret the phenotypes observed for these mutant strains. Naturally occurring sensors of hydrogen peroxide levels that are involved in regulation of gene expression will be studied. Levels of copper, zinc, manganese, and calcium metal ions will be determined in wild type and mutant strains in which levels of various antioxidant systems have been modified. Effects of addition or depletion of metal ions on the nature and rates of antioxidant and pro-oxidant processes and the maintenance of redox balance will be examined in the wild type and mutant strains as well. The roles played by the different metal ions will also be examined in yeast model systems designed to investigate processes related to aging, cell death and disease.

描述：生命在空气中是可能的，因为非催化反应的 生物体内的氧气通常是缓慢的。 此外，氧化 对健康细胞成分的损伤通常通过以下方式来防止或修复： 抗氧化剂，替代或修复系统，存在于细胞中， 维持和恢复氧化还原平衡。 我们的做法是 研究超氧化物，过氧化氢，金属离子和小分子的作用。 酵母S.啤酒。 酵母S.酿酒酵母 是一种简单的真核生物， 存在. 许多来自高等生物的基因已经被证明可以替代 功能上为他们的酵母类似物，更多的是预计现在整个 酵母基因组已经测序并可获得。 当生长在一个 非发酵性碳源，酵母细胞以一种 类似于人体细胞，以及用于预防、修复和修复的细胞系统 氧化损伤的细胞成分的替换也是类似的。 酵母 因此是研究氧化还原平衡如何 维持在健康的真核细胞中。 这些研究预计将导致 为了更好地理解真核生物的氧化还原平衡， "氧化应激"在导致人类衰老，细胞死亡， 和疾病 我们将确定超氧化物的主要天然来源， 酵母中过氧化氢，并测量其浓度和 细胞内的小分子抗氧化剂（还原和氧化）。 这些 方法将应用于野生型菌株和各种突变体 其中抗氧化系统和/或双氧代谢已被破坏的菌株 修改;结果将用于解释观察到的表型 这些突变株 天然存在的过氧化氢传感器 将研究参与基因表达调节的水平。 将测定铜、锌、锰和钙金属离子的水平 在野生型和突变株中， 系统已被修改。 金属离子添加或耗尽的影响 关于抗氧化剂和促氧化剂过程的性质和速率以及 将在野生型和突变体中检查氧化还原平衡的维持 菌株也是。 不同的金属离子所起的作用也将是 在酵母模型系统中进行了检查，旨在研究与 衰老细胞死亡和疾病