Sterol Transporters

Purinergic System Adenosine Receptors Sterol Transporters... 

Although no drugs directly targeting the sterol transporters described above are available, the function of several lipid lowering diugs is associated with interaction with ABCA1. 

T. Janvilisri, H. Venter, S. Shahi, G. Reuter, L. Balakrishnan, and H.W. Van Veen. Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 278 20645-20651 (2003). 

ApoE is also secreted by glia in the central nervous system and plays a role in sterol transport. The 4 allele is associated in a dose-dependent manner with early-onset Alzheimer s disease (see Chapter 60). 

Ezetimibe Blocks sterol transporter NPC1L1 in intestine brush border Inhibits reabsorption of cholesterol excreted in bile decreases LDL and phytosterols Elevated LDL, phytosterolemia Oral duration 24 h Toxicity Low incidence of hepatic dysfunction, myositis... 

Field, F.J., Bom, E., and Mathur, S.N. 2004. Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick Cl-like 1 protein gene expression. J. Lipid Res. 45, 2252-2259. 

BCRP is classified in ABCG subfamily other members of this subfamily are involved in sterol transport (269). Unlike P-gp and MRPs, BCRP consists of a single ABC cassette in the amino terminal followed by six putative transmembrane domains however, it forms a homodimer linked by a disulfide bond in the plasma membrane (270,271). Initially, ABCG2 was identified as an mRNA expressed in placenta (272) and as a non-MDRl- and non-MRP-type resistance factor from cell lines selected in the presence of anthracy-clines and mitoxantrone (273). BCRP is expressed widely in the normal tissues (274) and localized on the canalicular membrane of the hepatocytes and apical membranes of epithelial cells (274,275) and brain capillary endothelial cells (276,277). 

S. cerevisiae, the ABC transporters Ausl and Pdrl 1 are required for sterol uptake from media under anaerobic conditions. Interestingly, the C. glabrata AUSl homologue seems to function as a sterol transporter. However, in contrast to S. cerevisiae,... 

Metzler, L., Takano, Y, Chihana, H., and Niimi, M. (2007) The Candida glabrata putative sterol transporter gene CgAUSl protects cells against azoles in the presence of serum. The Journal of Antimicrobial Chemotherapy, 60, 1264-1272. 

Eukaryotic (putative) sterol transporter Niemann-Pick Cl like 1 Ezetimibe (inhibitor)... 

Huff, M.W., Pollex, R.L., Hegele, R.A. 2006. NPCILI evolution from pharmacological target to physiological sterol transporter. Arterioscler. Thromb. Vase. Biol. 26 2433-2438. 

Although there is abundant genetic evidence implicating ABC transporters in sterol transport, the precise mechanism of action is unknown. The simplest model predicts that sterols are the substrates for transporters that translocate the lipid across and out of a given... 

Maxfield, F.R., Menon, A.K. 2006. Intracellular sterol transport and distribution. Curr. Opin. Cell Biol. 18 379-385. 

Davis HR Jr, Altmann SW (2009) Niemann-Pick Cl Like 1 (NPCILI) an intestinal sterol transporter. Biochim Biophys Acta Mol Cell Biol Lipids 1791(7) 679-683. doi 10.1016/j. bbalip. 2009.01.002... 

Jain D, Ebine N, Jia X, et at. 2008. Corn Fiber Oil and Sitostanol Decrease Cholesterol Absorption Independently of Intestinal Sterol Transporters in Hamsters. The Journal of Nutritional Biochemistry 19(4) 229-236. 

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