Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
J Toxicol Environ Health B Crit Rev. 2009 Aug;12(7):540-51. doi: 10.1080/10937400903358975.
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.
谷胱甘肽结合物（GS-E）的转运是药物和环境污染物生物转化过程中产生的亲电化合物防御氧化/亲电性应激机制的核心。近年来，人们越来越关注 ABC 转运蛋白在 GS-E 的转运及其在解毒机制（包括耐药性）中的作用。然而，最近的研究表明，大多数人源和啮齿动物细胞中的 GS-E 转运是由一种非 ABC、多功能应激反应蛋白 RLIP76 或 RalBP1（ral 结合 GTP 酶激活蛋白 1）介导的，RLIP76 还作为 Ral-Ras-Rho 信号通路的效应物发挥作用。在简要描述谷胱甘肽（GSH）结合物转运领域的主要发现后，本文介绍了 RLIP76 在 GS-E 的 ATP 依赖性转运中的作用，以及该转运过程与外源性毒物、辐射和内源性亲电毒物的毒性机制的相关性。此外，还介绍了最近的研究表明 RLIP76 介导的 GS-E 转运与细胞周期信号之间存在联系。
