TY - JOUR
T1 - Physiological and pharmacological significance of glutathioneconjugate transport
AU - Awasthi, Yogesh C.
AU - Pankaj, Chaudhary
AU - Vatsyayan, Rit
AU - Abha, Sharma
AU - Awasthi, Sanjay
AU - Sharma, Rajendra
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77949496868&partnerID=8YFLogxK
U2 - 10.1080/10937400903358975
DO - 10.1080/10937400903358975
M3 - Review article
C2 - 20183533
AN - SCOPUS:77949496868
SN - 1093-7404
VL - 12
SP - 540
EP - 551
JO - Journal of Toxicology and Environmental Health - Part B: Critical Reviews
JF - Journal of Toxicology and Environmental Health - Part B: Critical Reviews
IS - 7
ER -