AGE-RELATED CHANGES IN GLUTATHIONE METABOLISM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 氧化应激被认为是导致特定疾病的开始或进展以及一般衰老过程的机制之一。谷胱甘肽(GSH)是一种存在于所有哺乳动物细胞中的高浓度三肽，是人体内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的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的综合现象，人们对可能调节全身和特定组织和细胞中GSH水平的潜在干预措施重新产生了兴趣。已知的年龄增长与氧化应激增加有关，据报道还与心血管疾病、糖耐量受损和糖尿病有关；后者也被证明伴随着较低的GSH浓度。可能导致谷胱甘肽状态受损的机制包括合成减少和/或相对于合成能力的利用增加。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GSH的多种途径，以及组织的多样性，使得对人类所有不同途径的利用进行有意义的同时测量是不可能的。因此，这项提案的重点将放在GSH合成率上。

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.