Liu R M, Shi M M, Giulivi C, Forman H J
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.
Am J Physiol. 1998 Mar;274(3):L330-6. doi: 10.1152/ajplung.1998.274.3.L330.
gamma-Glutamyl transpeptidase (GGT) plays an important role in glutathione (GSH) metabolism. GGT expression is increased in oxidant-challenged cells; however, the signaling mechanisms involved are uncertain. The present study used 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling quinone that continuously produced H2O2 in rat lung epithelial L2 cells. It was found that DMNQ increased GGT mRNA content by increasing transcription, as measured by nuclear run-on. This was accompanied by increased GGT specific activity. Cycloheximide, a protein synthesis inhibitor, blocked neither the increased GGT mRNA content nor the increased GGT transcription rate caused by DMNQ, suggesting that increased GGT transcription was a direct rather than secondary response. Previous data from this laboratory (R.-M. Liu, H. Hu, T. W. Robinson, and H. J. Forman. Am. J. Respir. Cell Mol. Biol. 14: 186-191, 1996) showed that tert-butylhydroquinone (TBHQ) increased GGT mRNA content by increasing its stability. TBHQ differs markedly from DMNQ in terms of its conjugation with GSH and H2O2 generation. Together, the data suggest that quinones upregulate GGT through multiple mechanisms, increased transcription and posttranscriptional modulation, which are apparently mediated through generation of reactive oxygen species and GSH conjugated formation, respectively.
γ-谷氨酰转肽酶（GGT）在谷胱甘肽（GSH）代谢中起重要作用。在受到氧化剂攻击的细胞中，GGT表达增加；然而，其中涉及的信号传导机制尚不清楚。本研究使用2,3-二甲氧基-1,4-萘醌（DMNQ），一种氧化还原循环醌，它在大鼠肺上皮L2细胞中持续产生过氧化氢。研究发现，如通过核转录实验所测，DMNQ通过增加转录来提高GGT mRNA含量。这伴随着GGT比活性的增加。蛋白质合成抑制剂环己酰亚胺既不阻断由DMNQ引起的GGT mRNA含量增加，也不阻断GGT转录速率增加，这表明GGT转录增加是一种直接反应而非次级反应。本实验室先前的数据（R.-M. Liu、H. Hu、T. W. Robinson和H. J. Forman。《美国呼吸细胞与分子生物学杂志》14: 186 - 191, 1996）表明，叔丁基对苯二酚（TBHQ）通过增加其稳定性来提高GGT mRNA含量。TBHQ在与GSH结合及过氧化氢生成方面与DMNQ明显不同。总之，数据表明醌类通过多种机制上调GGT，即增加转录和转录后调控，这显然分别通过活性氧的生成和GSH共轭物的形成介导。
