γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells
γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells
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DOI：
10.1016/j.lfs.2011.10.016
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发表时间：
2012-01-16
期刊：
影响因子：
6.1
通讯作者：
Omaye, Stanley T.
中科院分区：
文献类型：
--
作者：
Nakamura, Yukiko K.;Dubick, Michael A.;Omaye, Stanley T.
目的：γ-谷氨酰半胱氨酸（GGC）是一种二肽和抗氧化剂谷胱甘肽（GSH）合成的底物，其健康促进特性包括降低氧化应激相关损伤和疾病的风险。本研究的目的是探讨GGC对人内皮细胞GSH合成和氧化应激的影响。主要方法：我们评估了人脐静脉内皮细胞（HUVEC）的氧化应激、GSH、GSH合成酶（GSS）表达和转录因子DNA结合水平。与对照组相比，GSS蛋白、NF-κ B p65 DNA结合、硫代巴比妥酸反应物质（TBARS）和8-epi-PGF（2 α）呈浓度依赖性。GSH和GSS蛋白水平与PPAR γ DNA结合水平呈负相关，与NF-κ B p65 DNA结合、TBARS和8-epi-PGF（2 α）水平呈正相关趋势。在GSS基因转录起始位点上游4227个碱基处存在NF-κ B的结合位点，而未发现PPARs的结合位点。这些发现表明NF-κ B B参与了GSS表达的调节。随后的GSH合成可能会受到GSS表达的抑制在测试conditions.Significance：除了其在GSH合成中的底物作用，GGC可能发挥作用，作为一种抗氧化剂和调节蛋白质的表达，抗氧化防御保护免受氧化应激。因此，我们推测，GGC可能作为一种新的细胞内和细胞间治疗氧化应激相关的损伤和疾病的二肽。(C)2011 Elsevier Inc. All rights reserved.
Aims: gamma-Glutamylcysteine (GGC) is a dipeptide and substrate for synthesis of the antioxidant glutathione (GSH), whose health promoting properties include reducing risks of oxidative stress-related injuries and diseases. The objective of this study was to investigate the efficacy of GGC on GSH synthesis and oxidative stress in human endothelial cells.Main methods: We assessed oxidative stress, GSH, GSH synthetase (GSS) expression, and transcription factor DNA binding levels in human umbilical vein endothelial cells (HUVEC).Key findings: We found significantly higher levels of PPAR gamma DNA binding and lower levels of GSH. GSS protein, NF-kappa B p65 DNA binding, thiobarbituric acid reactive substances (TBARS), and 8-epi-PGF(2 alpha) in a concentration-dependent manner, compared with the control. GSH and GSS protein levels showed a negative correlation with PPAR gamma DNA binding levels and positive correlation trends with NF-kappa B p65 DNA binding, TBARS, and 8-epi-PGF(2 alpha) levels. A putative binding site for NF-kappa B was found at 4 227 bases upstream from the transcription start site of GSS gene, but none for PPARs. These findings suggest the involvement of NF-kappa B in regulation of GSS expression. Subsequent GSH synthesis might be affected by the suppression of GSS expression in tested conditions.Significance: Besides its substrate role in GSH synthesis, GGC may play a role in protection against oxidative stress by serving as an antioxidant and modulating the expression of protein(s) related to antioxidant defense. Thus, we speculate that GGC may serve as a novel intra- and intercellular therapeutic dipeptide for oxidative stress-related injuries and diseases. (C) 2011 Elsevier Inc. All rights reserved.