title: Glutathione S-transferase isoenzyme profile in non-tumor and tumor human kidney tissue.
abstract: Glutathione S-transferase (GST) isoenzyme profiles of non-tumor and tumor renal tissue of patients suffering from renal cell carcinoma (RCC) of the clear cell type were determined and compared to those of normal renal tissue. GST isoenzyme(s) were first separated on the basis of their affinity to glutathione sepharose 4B affinity column. Affinity-bound GSTs were further purified by anionic and cationic chromatofocusing. The results presented in this study show that non-tumor tissue distant from renal tumors and renal tumors have lower specific GST activity and a different isoenzyme profile than normal human kidney. Purification of normal kidney GSTs by affinity chromatography revealed the presence of two GST fractions: flow-through GST without affinity for glutathione affinity resin and GST fraction tightly bound to affinity matrix. In non-tumor kidney tissue of RCC patients, substantially less flow-through GST fraction was found, whereas renal tumors did not express flow-through GST at all. Isoelectric chromatofocusing indicated smaller numbers of GST isoenzymes in non-tumor and tumor kidney regions, with anionic forms dominating. It could be speculated that decreased expression of cationic GST isoenzymes (corresponding to class alpha) in non-tumor kidney tissue of RCC patients might be responsible for differences in sensitivity to specific carcinogens. The observations that RCCs are devoid of affinity flow-through GST and have small number of isoenzymes are further proof of low-level GST expression in RCC.
authors.affiliation: Institute of Biochemistry, University School of Medicine, Pasterova 2, 11000, Belgrade, Yugoslavia. tsimic@eunet.yu
authors.forename: Tatjana
authors.initials: T
authors.lastname: Simić
authors.forename: Jasmina
authors.initials: J
authors.lastname: Mimić-Oka
authors.forename: Katarina
authors.initials: K
authors.lastname: Ille
authors.forename: Dejan
authors.initials: D
authors.lastname: Dragicević
authors.forename: Ana
authors.initials: A
authors.lastname: Savić-Radojević
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000201:enzymology* / Q000628:therapy; D002846:Chromatography, Affinity; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D007668:Kidney / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology*; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000201:enzymology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D005982:Glutathione Transferase