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Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance.
Biochem Biophys Res Commun. 1995 Nov 02; 216(1):258-64.BB

Abstract

The ATP-dependent glutathione S-conjugate export pump (GS-X pump) has been suggested to play a role in the mechanism of cisplatin resistance. The purpose of this study was to determine the relationship between intracellular glutathione (GSH) levels and GS-X pump activity and whether GS-X pump overexpression results in cisplatin resistance. We transfected the human gamma-glutamylcysteine synthetase (gamma-GCS) gene into a human small-cell lung cancer cell line, SBC-3, producing SBC-3/GCS. The intracellular GSH content of SBC-3/GCS was twice that of the parental line, its GS-X pump activity was significantly enhanced and cellular cisplatin accumulation decreased. SBC-3/GCS showed higher resistance (relative resistance value of 7.4) to cisplatin than the parental line SBC-3. These data indicate that gamma-GCS gene overexpression induces cellular cisplatin resistance associated with increases in both the GSH content and GS-X pump activity, resulting in reduced cisplatin accumulation. In conclusion, GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance.

Authors+Show Affiliations

Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7488097

Citation

Kurokawa, H, et al. "Gamma-glutamylcysteine Synthetase Gene Overexpression Results in Increased Activity of the ATP-dependent Glutathione S-conjugate Export Pump and Cisplatin Resistance." Biochemical and Biophysical Research Communications, vol. 216, no. 1, 1995, pp. 258-64.
Kurokawa H, Ishida T, Nishio K, et al. Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance. Biochem Biophys Res Commun. 1995;216(1):258-64.
Kurokawa, H., Ishida, T., Nishio, K., Arioka, H., Sata, M., Fukumoto, H., Miura, M., & Saijo, N. (1995). Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance. Biochemical and Biophysical Research Communications, 216(1), 258-64.
Kurokawa H, et al. Gamma-glutamylcysteine Synthetase Gene Overexpression Results in Increased Activity of the ATP-dependent Glutathione S-conjugate Export Pump and Cisplatin Resistance. Biochem Biophys Res Commun. 1995 Nov 2;216(1):258-64. PubMed PMID: 7488097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gamma-glutamylcysteine synthetase gene overexpression results in increased activity of the ATP-dependent glutathione S-conjugate export pump and cisplatin resistance. AU - Kurokawa,H, AU - Ishida,T, AU - Nishio,K, AU - Arioka,H, AU - Sata,M, AU - Fukumoto,H, AU - Miura,M, AU - Saijo,N, PY - 1995/11/2/pubmed PY - 1995/11/2/medline PY - 1995/11/2/entrez SP - 258 EP - 64 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 216 IS - 1 N2 - The ATP-dependent glutathione S-conjugate export pump (GS-X pump) has been suggested to play a role in the mechanism of cisplatin resistance. The purpose of this study was to determine the relationship between intracellular glutathione (GSH) levels and GS-X pump activity and whether GS-X pump overexpression results in cisplatin resistance. We transfected the human gamma-glutamylcysteine synthetase (gamma-GCS) gene into a human small-cell lung cancer cell line, SBC-3, producing SBC-3/GCS. The intracellular GSH content of SBC-3/GCS was twice that of the parental line, its GS-X pump activity was significantly enhanced and cellular cisplatin accumulation decreased. SBC-3/GCS showed higher resistance (relative resistance value of 7.4) to cisplatin than the parental line SBC-3. These data indicate that gamma-GCS gene overexpression induces cellular cisplatin resistance associated with increases in both the GSH content and GS-X pump activity, resulting in reduced cisplatin accumulation. In conclusion, GS-X pump expression is related to cellular GSH metabolism and involved in cisplatin resistance. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/7488097/Gamma_glutamylcysteine_synthetase_gene_overexpression_results_in_increased_activity_of_the_ATP_dependent_glutathione_S_conjugate_export_pump_and_cisplatin_resistance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(85)72618-6 DB - PRIME DP - Unbound Medicine ER -