Physiological and pharmacological significance of glutathioneconjugate transport

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

Research output: Contribution to journalReview article

23 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)540-551
Number of pages12
JournalJournal of Toxicology and Environmental Health - Part B: Critical Reviews
Volume12
Issue number7
DOIs
StatePublished - 1 Dec 2009

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