Knickelbein R G, Ingbar D H, Seres T, Snow K, Johnston R B, Fayemi O, Gumkowski F, Jamieson J D, Warshaw J B
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):L115-22. doi: 10.1152/ajplung.1996.270.1.L115.
By participating in glutathione (GSH) synthesis, gamma-glutamyl transpeptidase (GGT) influences the GSH redox cycle, which is a major contributor in protecting against reactive oxygen metabolites. This study determined the effect of prolonged exposure of neonatal rats to > 98% oxygen on expression of GGT and on GSH metabolism. Lungs of neonatal rats chronically exposed to hyperoxia had increased expression of GGT mRNA, resulting in significantly higher GGT protein levels and enzyme activity than in lungs of animals raised in room air. Hyperoxia also upregulated glucose-6-phosphate dehydrogenase, but Na-K-ATPase activity was not changed. GGT mRNA, protein level, and enzyme activity returned to control levels after recovery in room air for 3 days. Levels of GSH, glutathione disulfide, and protein-bound GSH (S-glutathiolated protein) rose with hyperoxia and fell during recovery. S-glutathiolation is likely a mechanism for protection and a regulatory modification of protein sulfhydryl groups. Hyperoxia-induced upregulation of GGT and the concomitant increase in protein S-glutathiolation appear to be additional components fundamental in protecting the lung against oxidative injury.
γ-谷氨酰转肽酶（GGT）通过参与谷胱甘肽（GSH）合成影响GSH氧化还原循环，而GSH氧化还原循环是抵御活性氧代谢产物的主要因素。本研究确定了新生大鼠长期暴露于>98%氧气对GGT表达及GSH代谢的影响。长期暴露于高氧环境的新生大鼠肺组织中，GGT mRNA表达增加，导致GGT蛋白水平和酶活性显著高于在室内空气中饲养的动物肺组织。高氧还上调了葡萄糖-6-磷酸脱氢酶，但钠钾ATP酶活性未改变。在室内空气中恢复3天后，GGT mRNA、蛋白水平和酶活性恢复至对照水平。高氧时GSH、谷胱甘肽二硫化物和蛋白结合型GSH（S-谷胱硫基化蛋白）水平升高，恢复过程中下降。S-谷胱硫基化可能是一种保护机制以及对蛋白质巯基的调节修饰。高氧诱导的GGT上调以及随之而来的蛋白质S-谷胱硫基化增加似乎是肺组织抵御氧化损伤的另外两个重要因素。
