By Ahcene Boumendjel, Jean Boutonnat, Jacques Robert
A complete evaluate of the most up-tp-date clinical study on ABC transporters and multidrug resistanceATP-binding cassette transporter genes (ABC transporters) are recognized to play a very important position within the improvement of multidrug resistance (MDR). MDR is the power of pathologic cells, akin to tumors, to resist chemical substances designed to focus on and damage such cells. In MDR, sufferers who're on medicine finally advance resistance not to merely the drug they're taking, yet to a number of sorts of drugs.ABC Transporters and Multidrug Resistance deals an important source for pharmaceutical researchers who're operating to find medications to counteract multidrug resistance in ailments corresponding to melanoma. in a single complete quantity, this publication includes a number of the most up-tp-date wisdom at the involvement of ABC transporters in drug delivery and resistance.This entire quantity presents an summary at the description of the constitution, the genome, general tissue expression, physiological element, and mechanism of motion of the ABC protein. The professional members discover the expression, detection, and implications of ABC proteins in hematological malignancies and reliable 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 e-book bargains crucial details at the organic and medical point of multidrug resistance.
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Extra resources for ABC Transporters and Multidrug Resistance (Wiley Series in Drug Discovery and Development)
Szabó K, Bakos E, Welker E, Müller M, Goodfellow HR, Higgins CF et al. 1997. Phosphorylation site mutations in the human multidrug transporter modulate its drug-stimulated ATPase activity. J Biol Chem 272: 23165–23171. Ahmad S, Safa AR, and Glazer RI. 1994. Modulation of P-glycoprotein by protein kinase C alpha in a baculovirus expression system. Biochemistry 33: 10313– 10318. REFERENCES 41 80. Lelong-Rebel IH and Cardarelli CO. 2005. Differential phosphorylation patterns of P-glycoprotein reconstituted into a proteoliposome system: Insight into additional unconventional phosphorylation sites.
More generally, P-gp retains its function in liquid-ordered cholesterol and sphingolipid model membranes, and P-gp activity requires a microenvironment of raft microdomains or intermediate-density domains (162, 163). 3. Control and Regulation of Apoptosis A growing number of publications debate about the role of P-gp in apoptosis (164). Of course, due to its drug efflux function, P-gp exerts a strong downregulatory effect on drug-induced cell death, but it seems that this prevention 34 THE P-GLYCOPROTEIN 170 is not limited to this mechanism.
2. Lipid Transport In agreement with this flippase function, a growing number of publications have reported a role of P-gp in phospholipid translocation. P-gp has been reported to regulate the translocation of phosphatidylcholine and phosphatidylethanolamine, as well as sphingomyelin and several other short-chain phospholipid analogs (108, 153). This could explain in part the wide range of substrates recognized by P-gp, due to the different hydrophobic interactions inside lipid bilayers. More specifically, the simple glycosphingolipid (GlcCer) is a P-gp substrate candidate.