Physiological and pharmacological significance of glutathione-conjugate transport.

Yogesh C Awasthi, Pankaj Chaudhary, Rit Vatsyayan, Abha Sharma, Sanjay Awasthi, Rajendra Sharma

Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA. yawasthi@hsc.unt.edu

Journal of toxicology and environmental health. Part B, Critical reviews 2009 Aug

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Transport of the glutathione conjugates (GS-E) of electrophilic compounds generated during biotransformation of drugs and environmental pollutants is central to the mechanisms of defense against oxidative/electrophilic stress. In recent years emphasis has been placed on ATP-binding cassette (ABC) transport proteins in the transport of GS-E and their involvement in the detoxification mechanisms, including drug resistance. Recent studies, however, suggested that the majority of GS-E transport in human and rodent cells is mediated by a non-ABC, multifunctional stress-response protein, RLIP76 or RalBP1 (ral-binding GTPase activating protein 1), which also functions as an effector in the Ral-Ras-Rho signaling pathway. In this review, after briefly describing the major discoveries in the field of glutathione (GSH)-conjugate transport, recent findings are presented on the role of RLIP76 in ATP-dependent transport of GS-E, and the relevance of this transport process to the mechanisms of toxicity of xenobiotics, radiation, and endogenous electrophilic toxicants is described. Furthermore, recent studies suggesting a link between RLIP76 mediated GS-E transport and cell cycle signaling are presented.

Citation

Yogesh C Awasthi, Pankaj Chaudhary, Rit Vatsyayan, Abha Sharma, Sanjay Awasthi, Rajendra Sharma. Physiological and pharmacological significance of glutathione-conjugate transport. Journal of toxicology and environmental health. Part B, Critical reviews. 2009 Aug;12(7):540-51