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Abstract

Gamma glutamyltransferase (GGT) is a plasma membrane bound enzyme that initiates the degradation of glutathione. The presence of several promoters in the rat GGT gene indicates strict control and regulation of its expression. The aim of this study was to investigate whether the GGT gene was regulated differently after butyrate-induced differentiation and oxidative stress exposure of rat colon carcinoma cells and whether the regulation was related to the glutathione level. The activity of GGT was upregulated in a time-and-dose dependent manner after both butyrate and menadione incubations. The presence of antioxidants blocked the menadione but not the butyrate mediated induction of the enzyme. The level of intracellular glutathione was reduced after menadione, but not after butyrate incubations. Depletion of glutathione alone did not alter GGT activity. Reactive oxygen species (ROS) were not produced after incubations with butyrate, while menadione incubations produced ROS. The multiple GGT mRNA transcripts (mRNA I-V) that originate from the five distinct promoters were all present in the cell line. Incubations with butyrate enhanced mRNA II and IV transcripts whereas a reduction in mRNA IV-1 was noted during menadione incubations. The level of total GGT mRNA (I-V) was not altered when related to the amount of total beta-actin mRNA. We conclude that GGT activity can be upregulated by at least two distinct mechanisms during differentiation and oxidative stress. Apparently, the regulation of the enzyme is not directly linked to the intracellular level of glutathione.

Sensitive Fluorescence Probe with Long Analytical Wavelengths for γ-Glutamyl Transpeptidase Detection in Human Serum and Living Cells

“…A further use of the probe has been demonstrated by monitoring intracellular GGT level regulated by NaBu (a potential anticancer drug). As is known, NaBu has multiple effects on cell growth, differentiation and apoptosis, and thus its potential use is of great interest. − On the other hand, several GGT overexpressed cancer cells, such as melanoma, ovarian cancer cells, breast cancer cells (MCF-7), and colon carcinoma cells, could further upregulate the level of GGT after treatment with NaBu. − In consideration of the excellent performance of CV-Glu for visualizing GGT in living cells, we intend to explore the relationship between the GGT expression level and NaBu stimulation in HepG2 cells by using fluorescence imaging method.…”

“…[30][31][32][33][34] On the other hand, several GGT overexpressed cancer cells, such as melanoma, ovarian cancer cells, breast cancer cells (MCF-7) and colon carcinoma cells, could further upregulate the level of GGT after treatment with NaBu. [35][36][37] In consideration of the excellent performance of CV-Glu for visualizing GGT in living cells, we intend to explore the relationship between GGT expression level and NaBu stimulation in HepG2 cells by using fluorescence imaging method. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Prior to such an attempt, the influence of NaBu on both the fluorescence of CV-Glu and the activity of GGT was first examined.…”

Gamma-Glutamyl Transpeptidase

“…A time- and dose-dependent increase in GGT mRNA and GGT activity was reported in CC531 rat colon carcinoma cells exposed to ionizing radiation, which caused the formation of reactive oxygen and nitrogen species (Pankiv, Moller, Bjorkoy, Moens, & Huseby, 2006). In the same cell line, menadione treatment induced both ROS and GGT activity (Mikkelsen, Mortensen, Laperche, & Huseby, 2002). In a subsequent study, the authors reported that ROS induced GGT involved activation of Ras and was mediated through an AKT, p38 MAPK and MEK1 dependent pathway (Pandur, Pankiv, Johannessen, Moens, & Huseby, 2007).…”