Tissue glutathione and cysteine levels in methionine-restricted rats
Tissue glutathione and cysteine levels in methionine-restricted rats
复制标题
DOI：
10.1016/j.nut.2004.05.009
复制
发表时间：
2004-09-01
期刊：
影响因子：
4.4
通讯作者：
Zimmerman, JA
中科院分区：
文献类型：
--
作者：
Richie, JP;Komninou, D;Zimmerman, JA
目的：之前，我们证明终身蛋氨酸（Met）限制（MR）可以延长大鼠的寿命，降低衰老相关疾病的发病率，增加血液谷胱甘肽（GSH）水平，并防止GSH在衰老过程中的损失。我们目前的目的是通过确定年轻和成熟大鼠血液和其他组织中谷胱甘肽和半胱氨酸变化的时间过程和性质来阐明MR对谷胱甘肽代谢和运输的影响。方法：雄性F-344大鼠在7周龄时饲喂对照（蛋氨酸含量为0.86%）或MR（蛋氨酸含量为0.17%）氨基酸饲料，并在不同时间处死。成年（12岁）大鼠也开始进行MR。结果：在MR治疗的前2个月，与对照组相比，血液GSH水平上升84%，肝脏GSH水平下降66%。在这段时间之后，肝脏GSH水平在至少6个月内保持不变。胰腺（80%）和肾脏（22%）的GSH水平也有所下降，但在MR 11周后检查的其他组织中GSH水平保持不变。在MR开始后1周，血液GSH明显升高，并在6周达到平台期。当给成年大鼠注射MR时，观察到红细胞GSH水平也有类似的增加。在对照组中，禁食降低了肝脏GSH，但在MR动物中没有进一步的影响。1个月时，除脑外所有组织的半胱氨酸水平均下降。结论：这些结果表明，在年轻和成年大鼠中，MR导致Met、半胱氨酸和/或谷胱甘肽代谢发生适应性变化。这些早期代谢变化导致大多数肝外组织中谷胱甘肽水平的保持，并通过消耗肝脏谷胱甘肽至临界水平而增加红细胞中的谷胱甘肽。(C) Elsevier Inc., 2004。
OBJECTIVE: Previously, we demonstrated that lifelong methionine (Met) restriction (MR) increases lifespan, decreases the incidence of aging-related diseases, increases blood glutathione (GSH) levels, and prevents loss of GSH during aging in rats. Our present objective was to elucidate the effects of MR on GSH metabolism and transport by determining the time course and nature of GSH and cysteine changes in blood and other tissues in young and mature rats.METHODS: Male F-344 rats were placed on control (0.86% Met) or MR (0.17% Met) defined amino acid diets at age 7 wk and killed at different times thereafter. MR was also initiated in adult (12-mo-old) rats.RESULTS: Throughout the first 2 mo of MR, blood GSH levels increased 84% and liver GSH decreased 66% in relation to controls. After this period, liver GSH levels remained constant through at least 6 mo. GSH levels also decreased in the pancreas (80%) and kidney (22%) but remained unchanged in other tissues examined after 11 wk of MR. The, increase in blood GSH was evident as soon as 1 wk after initiating MR and reached a plateau by 6 wk. A similar increase in erythrocyte GSH levels was observed when MR was administered to mature adult rats. Fasting decreased liver GSH in controls but had no further effect in MR animals. By 1 mo, cysteine levels had decreased in all tissues except brain.CONCLUSION: These results suggest that adaptive changes occur in the metabolism of Met, cysteine, and/or GSH as a result of MR in young and adult rats. These early metabolic changes lead to conservation of GSH levels in most extrahepatic tissues and increased GSH in erythrocytes by depleting liver GSH to a critical level. (C) Elsevier Inc. 2004.