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AGING EFFECT ON PROTEIN S THIOLATION/DETHIOLATION

老化对蛋白质硫醇化/脱硫醇化的影响

基本信息

批准号：
2409879
负责人：
JAMES Alanson THOMAS
金额：
$ 7.09万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-07-15 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2409879
关键词：
aging animal old age antioxidants carbonate dehydratase cysteine electrofocusing enzyme linked immunosorbent assay genetic transcription glutathione laboratory rat liver metabolism oxidative stress protein metabolism protein structure function redoxin sulfhydration thiols thioredoxin

项目摘要

Our long term goal is to understand the function of the protein antioxidant system that protects reactive protein sulfhydryl groups from oxidative damage, i.e, the protein S-thiolation/ dethiolation protection system. This application is a one year pilot project to investigate the role of protein S-thiolation/dethiolation in an aging animal model. We will I) determine whether aging causes increased protein S-thiolation in rats, identifying individual modified proteins by a newly proposed method, and whether irreversibly modified forms of carbonic anhydrase III are a consequence of inadequate protection by S-thiolation/dethiolation; 2) determine whether the dethiolation system, i.e., glutaredoxin and thioredoxin, is less effective as a consequence of aging; and 3) develop a method to produce an antibody to glutathione that can be used to detect protein-bound glutathione, i.e., S-glutathiolated proteins, in future experiments. These experiments are our first attempt to relate the function of the protein antioxidant system (S-thiolation/dethiolation) to altered signal transduction, and gene transcription in an aging animal model. The proposal is based on a recent report of increased S-glutathiolation of carbonic anhydrase III in the liver of older rats. This unique result suggests that the protein antioxidant system is less effective in older animals, potentially leading to irreversible modification (oxidation) of these proteins as well as increased S-thiolation of a number o important protein cysteines. Since we propose that the cysteines required for lipidation, ADP-ribosylation, cysteine- mediated proteolysis in apoptosis, and redox control of transcription are all protected by the S-thiolation/dethiolation antioxidant system, any loss of the protective role it performs would certainly be detrimental to proper cell functions in aged animals. The experiments describe methods to assess both protein S- thiolation and irreversible oxidation in older animals.

我们的长期目标是了解蛋白质的功能保护活性蛋白巯基的抗氧化系统氧化损伤，即蛋白质S-硫醇化/脱硫醇化保护系统此应用程序是一个为期一年的试点项目，研究蛋白质S-硫醇化/脱硫醇化在一种衰老动物模型 We will I）determine whether老化causes原因大鼠中蛋白S-巯基化增加，鉴别个体通过新提出的方法修饰蛋白质，以及是否碳酸酐酶III的不可逆修饰形式是 S-硫醇化/脱硫醇化保护不足的结果; 2)确定脱硫系统，即，谷氧还蛋白和硫氧还蛋白，由于老化而不太有效;并且 3)开发一种方法来生产谷胱甘肽的抗体，用于检测蛋白结合的谷胱甘肽，即，S-谷胱甘肽化蛋白质在未来的实验中这些实验是我们第一次试图将蛋白质抗氧化系统的功能（S-硫醇化/脱硫醇化）改变信号转导，和衰老动物模型中的基因转录。所涉提议主要最近有报道称，老年大鼠肝脏中的脱水酶III。这个独特的结果表明蛋白质抗氧化系统在年龄较大的动物，可能导致不可逆的改变这些蛋白质的S-巯基化增加，许多重要的蛋白质半胱氨酸。既然我们建议脂化、ADP-核糖基化、半胱氨酸- 介导的蛋白水解在细胞凋亡中的作用，转录都受到S-巯基化/脱巯基化的保护抗氧化系统，任何损失的保护作用，它执行对老年人正常的细胞功能肯定是有害的。动物实验描述了评估蛋白S- 老年动物中的硫醇化和不可逆氧化。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Regulation of FSH receptor promoter activation in the osteoclast.

破骨细胞中 FSH 受体启动子激活的调节。

DOI：
10.1016/j.bbrc.2007.07.081
发表时间：
2007
期刊：
Biochemical and biophysical research communications
影响因子：
3.1
作者：
Zaidi,Samir;Zhu,Ling-Ling;Mali,Rajesh;Iqbal,Jameel;Yang,Guozhe;Zaidi,Mone;Sun,Li
通讯作者：
Sun,Li

Skeletal morphofunctional considerations and the pituitary-thyroid axis.

骨骼形态功能考虑因素和垂体甲状腺轴。

DOI：
10.2741/s9
发表时间：
2009
期刊：
Frontiers in bioscience (Scholar edition)
影响因子：
0
作者：
Iqbal,Jameel;Davies,TerryF;Sun,Li;Abe,Etsuko;Carpi,Angelo;Mechanick,JeffreyI;Zaidi,Mone
通讯作者：
Zaidi,Mone

CD38 is required for priming by TNF-alpha: a mechanism for extracellular coordination of cell fate.

CD38 是 TNF-α 启动所必需的：TNF-α 是细胞命运的细胞外协调机制。