Transport functions and physiological significance of 76 kDa Ral-binding GTPase activating protein [RLIP76]

• Autorzy: Awasthi S. , Sharma R. , Yang Y. , Singhal S.S. , Pikula S. , Bandorowicz-Pikula J. , Singh S.V. , Zimniak P. , Awasthi Y.C.
• Języki publikacji: EN

Abstrakty

EN

We have recently demonstrated that a previously known Ral-binding GTPase acti­vating protein, RLIP76, can also catalyze ATP-dependent transport of various struc­turally unrelated xeno- and endobiotics irrespective of their net charge (Awasthi etal., 2000, Biochemistry, 39: 9327). RLIP76 is a non-ATP binding cassette (ABC) protein but it has two ATP-binding sites and shows basal ATPase activity which is stimulated in the presence of its transport substrates (allocrites) such as doxorubicin (DOX) and S-(2,4-dinitrophenyl) glutathione (DNP-SG). Proteoliposomes reconstituted with purified RLIP76 catalyze ATP-dependent, saturable transport of DOX, as well as of glutathione-conjugates including leukotrienes (LTC4) and the GSH-conjugate of 4-hydroxynonenal (GS-HNE). In erythrocytes the majority of transport activity for DOX, GS-HNE, and LTC4 is accounted for by RLIP76. Cells exposed to mild oxidative stress show a rapid and transient induction of RLIP76 resulting in an increased efflux of GS-HNE and acquire resistance to oxidative stress mediated toxicity and apoptosis. Cells transfected with RLIP76 acquire resistance to DOX through increased efflux of the drug suggesting its possible role in the mechanisms of drug-resistance. In this article, we discuss the significance of transport functions of RLIP76 highlighting its role in the defense mechanisms against oxidative injury, and modulation of signaling mechanisms.

Słowa kluczowe

EN

cytochrome; multidrug resistance; xenobiotic; transport function; enzyme; biotransformation; protein; glutathione conjugation; GTPase

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2002
• Tom: 49
• Numer: 4
• Opis fizyczny: p.855-867,fig.

Twórcy

autor

Awasthi S.

• University of Texas at Arlington, Arlington TX, USA

autor

Sharma R.

autor

Yang Y.

autor

Singhal S.S.

autor

Pikula S.

autor

Bandorowicz-Pikula J.

autor

Singh S.V.

autor

Zimniak P.

autor

Awasthi Y.C.

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