Liu Rui-Ming, Dickinson Dale A
Department of Environmental Health Sciences and Center for Free Radical Biology, University of Alabama at Birmingham School of Public Health, Birmingham, AL 35294-0022, USA.
Antioxid Redox Signal. 2003 Oct;5(5):529-36. doi: 10.1089/152308603770310176.
Although it is well documented that the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, declines with age in many tissues of different animal species, the underlying mechanism is not well understood. In a previous study, we showed that the expression of the glutamate cysteine ligase genes was down-regulated with age, accompanied by a decline in GSH content in the liver, kidney, and lung of Fisher 344 rats. The aim of this study was to examine the age-associated changes in the activities of three other enzymes, which also play important roles in GSH biosynthesis, to further explore the mechanism underlying the age-associated decline in GSH content in Fisher 344 rats. The results showed for the first time that the activity and gene expression of glutathione synthase, which catalyzes the second reaction in de novo GSH synthesis, were also decreased with increased age in the lung and kidney, but not in the liver or heart. No age-associated change in the activity of either gamma-glutamyltranspeptidase or glutathione reductase was observed in any of the organs examined. The results further indicate that decreased GSH synthetic capacity is responsible for the age-associated decline in GSH content in Fisher 344 rats.
尽管有充分的文献记载，谷胱甘肽（GSH）是细胞内最丰富的游离硫醇和重要的抗氧化剂，其在不同动物物种的许多组织中的浓度会随着年龄的增长而下降，但其潜在机制尚未完全了解。在先前的一项研究中，我们发现谷氨酸半胱氨酸连接酶基因的表达随年龄增长而下调，同时Fisher 344大鼠肝脏、肾脏和肺中的谷胱甘肽含量也随之下降。本研究的目的是检测其他三种在谷胱甘肽生物合成中也起重要作用的酶的活性随年龄的变化，以进一步探究Fisher 344大鼠体内谷胱甘肽含量随年龄下降的潜在机制。结果首次表明，催化从头合成谷胱甘肽中第二步反应的谷胱甘肽合酶的活性和基因表达，在肺和肾脏中也随着年龄的增长而降低，但在肝脏或心脏中未出现这种情况。在所检测的任何器官中，均未观察到γ-谷氨酰转肽酶或谷胱甘肽还原酶的活性随年龄发生变化。这些结果进一步表明，谷胱甘肽合成能力的下降是Fisher 344大鼠体内谷胱甘肽含量随年龄下降的原因。
