AGE-RELATED CHANGES IN GLUTATHIONE METABOLISM

谷胱甘肽代谢与年龄相关的变化

• 批准号: 7378574
• 负责人: NAOMI K FUKAGAWA
• 金额: $ 3.46万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-09 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378574
• 关键词: aging; antioxidants; detoxification; diabetes mellitus; glutathione; human; lead; measurement; metabolism; motivation; oxidative stress; oxidizing agents; play; role; thinking; tissues

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. Oxidative stress is thought to be one of the mechanisms leading to the initiation or progression of specific diseases as well as to the general process of aging. Glutathione (GSH), a tripeptide present in high concentrations in all mammalian cells, is the body's major endogenous antioxidant and plays a vital role in detoxification reactions and in the protection of cells from the toxic effects of oxidants. Maintenance of body GSH stores is a complex, integrated phenomenon, and there has been a resurgence of interest in potential interventions that may modulate GSH levels in the whole body and in specific tissues and cells. Advancing age, known to be associated with increased oxidative stress, is also reported to be associated with cardiovascular disease, impaired glucose tolerance, and diabetes mellitus; the latter has also been shown to be accompanied by lower GSH concentrations. The mechanisms that could be responsible for a compromised GSH status include decreased synthesis and/or increased utilization relative to synthetic capacity. Ideally, one would like to measure in vivo rates of both GSH synthesis and utilization. Unfortunately, the multitude of pathways consuming GSH, as well as tissue variation, makes it impossible to have meaningful simultaneous measurements of utilization by all of the different pathways in the human. Hence, the focus of this proposal will be on GSH synthesis rates.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。氧化应激被认为是导致特定疾病发生或进展以及一般衰老过程的机制之一。谷胱甘肽 (GSH) 是一种高浓度存在于所有哺乳动物细胞中的三肽，是人体主要的内源性抗氧化剂，在解毒反应和保护细胞免受氧化剂毒性作用中发挥着至关重要的作用。体内 GSH 储存的维持是一个复杂、综合的现象，人们对可能调节全身以及特定组织和细胞中 GSH 水平的潜在干预措施重新产生了兴趣。据报道，年龄增长与氧化应激增加有关，也与心血管疾病、糖耐量受损和糖尿病有关。后者也被证明伴随着较低的谷胱甘肽浓度。可能导致 GSH 状态受损的机制包括相对于合成能力的合成减少和/或利用率增加。理想情况下，人们希望测量体内 GSH 合成和利用的速率。不幸的是，消耗谷胱甘肽的途径众多，以及组织变异，使得不可能对人体中所有不同途径的利用进行有意义的同时测量。因此，该提案的重点将是 GSH 合成率。