By Ahcène Boumendjel, Jean Boutonnat, Jacques Robert
A accomplished evaluation of the most up-tp-date medical examine on ABC transporters and multidrug resistance
ATP-binding cassette transporter genes (ABC transporters) are identified to play a vital function within the improvement of multidrug resistance (MDR). MDR is the power of pathologic cells, resembling tumors, to resist chemical substances designed to focus on and ruin such cells. In MDR, sufferers who're on medicine ultimately improve resistance not to purely the drug they're taking, yet to a number of types of drugs.
ABC Transporters and Multidrug Resistance bargains a vital source for pharmaceutical researchers who're operating to find medications to counteract multidrug resistance in ailments corresponding to melanoma. in a single entire quantity, this booklet incorporates a choice of the most up-tp-date wisdom at the involvement of ABC transporters in drug shipping and resistance.
This finished quantity offers an outline at the description of the constitution, the genome, common tissue expression, physiological point, and mechanism of motion of the ABC protein. The professional participants discover the expression, detection, and implications of ABC proteins in hematological malignancies and good tumors and ABC proteins and pathogenic microorganisms. This quantity additionally explains MDR modulation via inhibition of ABC transporters and the layout of inhibitors and mechanism of motion. moreover, the ebook deals crucial details at the organic and medical point of multidrug resistance.
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Additional info for ABC Transporters and Multidrug Resistance
Enhancement of ABCB1 expression constitutes one part of the response. 2. Cellular Localization of P-gp Numerous studies have suggested a different intracellular localization of cytotoxic drugs between sensitive and MDR cells (116–120). Most of the drug accumulates in the nucleus of sensitive cells. In MDR cells overexpressing P-gp, the protein is mainly located in the plasma membranes of the cells, and altered drug distribution has been observed in resistant cells. The drug is largely excluded from the nuclei and is sequestered in perinuclear vesicles that move toward the cell periphery to create punctate cytoplasmic distribution patterns (121).
In the “ﬂippase” model, P-gp encounters drugs in the inner leaﬂet of the plasma membrane and ﬂips them to the outer leaﬂet from which they diffuse into the extracellular medium (149). This model is based on the analogy between amphipathic drugs and the normal phospholipids of membranes. Whereas the lateral mobility of phospholipids within the membrane is high, the spontaneous rate of ﬂipping between the two leaﬂets of the membrane is very low because the polar-heads groups of the phospholipids cannot be easily transferred across the hydrophobic internal part of the membrane, which is constituted by the acyl chains of the phospholipids.
Biochim Biophys Acta 1172: 138–146. 21. Huff LM, Wang Z, Iglesias A, Fojo T, and Lee JS. 2005. Aberrant transcription from an unrelated promoter can result in MDR-1 expression following drug selection in vitro and in relapsed lymphoma samples. Cancer Res 65: 11694–11703. 22. Lutterbach B, Sun D, Schuetz J, and Hiebert SW. 1998. The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein. Mol Cell Biol 18: 3604–3611. REFERENCES 37 23.
ABC Transporters and Multidrug Resistance by Ahcène Boumendjel, Jean Boutonnat, Jacques Robert