Tumor Biology Research Group, Faculty of Health Sciences, University of Tromsø, Norway.
Free Radic Res. 2011 May;45(5):600-10. doi: 10.3109/10715762.2011.564164. Epub 2011 Mar 7.
γ-Glutamyltransferase (GGT) plays a significant role in antioxidant defence and participates in the metabolism of glutathione (GSH). The enzyme is up-regulated after acute oxidative stress and during pro-oxidant periods, but the underlying regulatory mechanisms are not well known. The present investigation studied whether the endogenous reactive oxygen species (ROS) level was a determinant for GGT expression. A substantial amount of ROS is produced through the NADPH oxidase (NOX) system and knockdown of p22phox, a sub-unit of NOX1-4, resulted not only in reduced ROS levels but also in reduced GGT expression in human endometrial carcinoma cells. Phorbol-12-myristate-13-acetate (PMA) is an activator of NOX and it was found that PMA treatment of human colon carcinoma cells both increased cellular ROS levels and subsequently up-regulated GGT expression. On the other hand, the NOX inhibitor apocynin reduced ROS levels as well as GGT expression. The GGT mRNA sub-type A was increased after PMA-induced NOX activation. These results demonstrate that ROS generated from NOX enzymes are a significant determinant for GGT expression and activity.
γ-谷氨酰转移酶（GGT）在抗氧化防御中发挥重要作用，并参与谷胱甘肽（GSH）的代谢。该酶在急性氧化应激和促氧化剂期间上调，但潜在的调节机制尚不清楚。本研究探讨了内源性活性氧（ROS）水平是否是 GGT 表达的决定因素。大量的 ROS 通过 NADPH 氧化酶（NOX）系统产生，并且敲低 NOX1-4 的亚单位 p22phox，不仅导致 ROS 水平降低，而且导致人子宫内膜癌细胞中的 GGT 表达降低。佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）是 NOX 的激活剂，发现 PMA 处理人结肠癌细胞既增加了细胞内 ROS 水平，随后又上调了 GGT 表达。另一方面，NOX 抑制剂 apocynin 降低了 ROS 水平和 GGT 表达。PMA 诱导的 NOX 激活后，GGT mRNA 亚型 A 增加。这些结果表明，来自 NOX 酶的 ROS 是 GGT 表达和活性的重要决定因素。
