Physiological and pharmacological significance of glutathioneconjugate transport

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

Research output: Contribution to journalReview article

20 Citations (Scopus)

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

Fingerprint

Glutathione
Carrier Proteins
Adenosine Triphosphate
Pharmacology
GTPase-Activating Proteins
Environmental Pollutants
Detoxification
Oxidative stress
Xenobiotics
Protein Transport
Biotransformation
Heat-Shock Proteins
Drug Resistance
Pharmaceutical Preparations
Toxicity
Rodentia
Cell Cycle
Oxidative Stress
Cells
Radiation

Cite this

Awasthi, Yogesh C. ; Chaudhary, Pankaj ; Vatsyayan, Rit ; Abha, Sharma ; Awasthi, Sanjay ; Sharma, Rajendra. / Physiological and pharmacological significance of glutathioneconjugate transport. In: Journal of Toxicology and Environmental Health - Part B: Critical Reviews. 2009 ; Vol. 12, No. 7. pp. 540-551.
@article{a4c3b456cbee4b49a393ec94e466f08c,
title = "Physiological and pharmacological significance of glutathioneconjugate transport",
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.",
author = "Awasthi, {Yogesh C.} and Pankaj Chaudhary and Rit Vatsyayan and Sharma Abha and Sanjay Awasthi and Rajendra Sharma",
year = "2009",
month = "12",
day = "1",
doi = "10.1080/10937400903358975",
language = "English",
volume = "12",
pages = "540--551",
journal = "Journal of Toxicology and Environmental Health - Part B: Critical Reviews",
issn = "1093-7404",
publisher = "Taylor and Francis Ltd.",
number = "7",

}

Physiological and pharmacological significance of glutathioneconjugate transport. / Awasthi, Yogesh C.; Chaudhary, Pankaj; Vatsyayan, Rit; Abha, Sharma; Awasthi, Sanjay; Sharma, Rajendra.

In: Journal of Toxicology and Environmental Health - Part B: Critical Reviews, Vol. 12, No. 7, 01.12.2009, p. 540-551.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Physiological and pharmacological significance of glutathioneconjugate transport

AU - Awasthi, Yogesh C.

AU - Chaudhary, Pankaj

AU - Vatsyayan, Rit

AU - Abha, Sharma

AU - Awasthi, Sanjay

AU - Sharma, Rajendra

PY - 2009/12/1

Y1 - 2009/12/1

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

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

SN - 1093-7404

IS - 7

ER -