Selective expression of glutathione transferase isoenzymes in chemically induced preneoplastic rat heptocyte nodules

Abstract

Isoenzymes of glutathione transferase were shown to occur at selectively altered levels in rat hepatocyte nodules produced by 2-acetylaminofluorene treatment. Changes were measured by different substrates, antibodies raised against purified glutathione transferases, and by purification of the major isoenzymes. Isoenzymes composed of subunits 1,2 and 3, expressed in normal liver tissue, all occurred at increased concentrations in nodules, whereas the level of transferase 4-4 was decreased. The most conspicuous change was the appearance of glutathione transferase 7-7 (or transferase P), the concentration of which in negligible in normal liver. Glutathione transferase Hepatocyte nodule Isoenzyme induction Preneoplastic marker Immunoprecipitation

.GAMMA.-Glutamyl Transpeptidase, Glutathione S-Transferase, Alkaline Phosphatase, and Glutathione Levels during Different Stages of Chemically Induced Hepatocarcinogenesis in the Rat.

“…A more accurate measure would be to determine specific ALP isoenzyme activities in the affected tissue itself, preferably by electrophoretic methods [27]. Glutathione S-transferase activities in the liver of the treated rats were also higher than those for the controls, in accordance with the results of Jensson et al [7]. There tended to be a decrease with time in the activities in the treated rats.…”

“…Gross morphological changes, which are usually not observed during the early stages of hepatocarcinogenesis, become apparent after the tissue has been transformed. Tumor marker enzymes such as y-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), and the placental form of glutathione S-transferase (PGST) have been found to be useful in the detection and monitoring of the progression of carcinogenesis [2][3][4][5][6][7][8]. The change in the expression of these enzymes is usually a reflection of the change in the tissue, and the correlation of these enzyme activities with carcinogenesis is evident.…”

“…Elevated activities of GGT have been strongly correlated with the extent of carcinogenesis [9]. The expression of variant ALP isoenzymes has been shown in various cancers [10], and the selective expression of PGST has been shown to occur during the preneoplastic state [7]. Since the activities of such tumor marker enzymes have been reported to increase in chemically induced carcinogenesis, the determination of these activities provides a useful method for monitoring the progress of hepatocarcinogenesis.…”

Metabolism of Xenobiotics in Hepatocyte Nodules

“…Jensson et a1 investigated the isoenzyme composition of hepatocyte nodules produced by intermittent feeding of 2-acetylaminofluorene (42). The work describes the purification, identification, and quantitation of cytosolic peptides with glutathione transferase activity that is retained on an S-hexylglutathione-Sepharose-6B affinity matrix.…”

Activation of rat hepatic stellate cells leads to loss of glutathionS-transferases and their enzymatic activity against products of oxidative stress

“…In fact, the expression of alpha and mu class GSTs is increased in chemically transformed hepatocytes and there is de novo expression of rGSTP1. 41 Therefore, HSCs provide a unique model for the investigation of how GST genes are negatively regulated at the transcriptional and translational levels.…”