Rui-Ming Liu, Ph.D.
Molecular Pharmacology and Toxicology
g-Glutamyl transpeptidase, tumors and oxidative stress
Development of drug resistance in tumor cells is a major obstacle in tumor treatment. Several mechanisms have been described that mediate such resistance. One of these mechanisms is increased detoxification processes such as increased conjugation of GSH with the drugs followed by increased drug efflux from the tumor cells.
g-Glutamyl transpeptidase (gGT), a membrane bound enzyme, plays an important role in glutathione metabolism by breaking down the extracellular GSH and providing the cells with amino acids or dipeptide for GSH synthesis. Data from our lab have shown that the expression of gGT in rat lung epithelial L2 cells is increased by oxidative stress and gGT has a very important role in maintaining intracellular GSH level for both resting cells and oxidatively challenged cells. By measuring the gGT activity and mRNA level in different neuroblastoma cell lines obtained from different stages of patients we found that the tumor cells from the relapsed tumor contained higher gGT activity and mRNA level than those obtained before chemotherapeutic treatment. We will continue to study whether this increased expression of gGT is involved in the increased resistance of these tumor cells to the chemotherapeutic agents. Since gGT has been shown inducible by oxidative stress we would also like to know whether the increased expression of gGT is due to the high level of oxidative status in these tumor cells.
Selected Publications
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