Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among tumoral resistances, multidrug resistance (MDR) is characterized as cross-resistance to a variety of structurally and functionally unrelated drugs such as vinca alkaloids, colchicine, and anthracyclines. Decreased drug cellular influx and increased cellular ability for drug extrusion are the main mechanisms involved in MDR. Two plasma membrane proteins, p-glycoprotein (p-gp) and the multidrug resistance-associated protein (MRP), act as ATP-dependent cellular efflux. Furthermore, protein kinase C (PKC) is also central to MDR. The present study reviews the role of cholesterol and other lipids in the reduction of drug influx and drug binding to cellular membranes. The study also examines the effect of lipid composition on p-gp activity. Concerning the role of PKC in MDR, two phospholipases involved in diacylglycerol (DG) production increase in MDR cells. These are phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C and phosphatidylethanolamine-specific phospholipase D. A positive feedback mechanism for DG production which includes these phospholipases, a phosphatidylcholine-specific phospholipase C and a phosphatidylcholine-specific phospholipase A2 has also been suggested. The hypothesis of exocytic involvement in MDR is reviewed, and some lipid changes found in MDR cells are interpreted according to those fusogenic properties normally involved in exocytic transport. Also, the possible role of lipid mediators, such as phosphatidic acid and platelet-activating factor, is examined.
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PMID:Lipids: A key role in multidrug resistance? (Review). 1071 49

Calcium entry is one of the main regulators of intracellular signaling. Here, we have described the importance of sphingosine, sphingosine kinase 1 (SK1), and sphingosine 1-phosphate (S1P) in regulating calcium entry in thyroid FRTL-5 cells. In cells incubated with the phosphatase inhibitor calyculin A, which evokes calcium entry without mobilizing sequestered intracellular calcium, sphingosine inhibited calcium entry in a concentration-dependent manner. Furthermore, inhibiting SK1 or the ATP-binding cassette ABCC1 multidrug transporter attenuated calcium entry. The addition of exogenous S1P restored calcium entry. Neither sphingosine nor inhibition of SK1 attenuated thapsigargin-evoked calcium entry. Blocking S1P receptor 2 or phospholipase C attenuated calcium entry, whereas blocking S1P receptor 3 did not. Overexpression of wild-type SK1, but not SK2, enhanced calyculin-evoked calcium entry compared with mock-transfected cells, whereas calcium entry was decreased in cells transfected with the dominant-negative G82D SK1 mutant. Exogenous S1P restored calcium entry in G82D cells. Our results suggest that the calcium entry pathway is blocked by sphingosine and that activation of SK1 and the production of S1P, through an autocrine mechanism, facilitate calcium entry through activation of S1P receptor 2. This is a novel mechanism by which the sphingosine-S1P rheostat regulates cellular calcium homeostasis.
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PMID:Sphingosine kinase as a regulator of calcium entry through autocrine sphingosine 1-phosphate signaling in thyroid FRTL-5 cells. 1979 3