Steroid-derived phospholipid scramblases induce exposure of phosphatidylserine on the surface of red blood cells.
A series of methyl 7alpha,12alpha-bis(phenylurea) cholate derivatives with different cationic substituents at the 3alpha-position were prepared and evaluated for an ability to increase the level of endogenous phosphatidylserine (PS) on the surface of red blood cells (erythrocytes). Some of the compounds induced large fractions of erythrocytes to expose sufficient PS to become stained by the protein annexin V-FITC. In addition, the compounds were found to bind PS in homogeneous solution, and to promote the translocation of fluorescent NBD-labeled phospholipids across vesicle membranes, which supports the hypothesis that cholate-induced exposure of endogenous PS on the erythrocyte surface is due to the ability of the cationic cholates to promote anionic phospholipid flip-flop.
DiVittorio
Kristy M
KM
Department of Chemistry and Biochemistry and the Walther Cancer Research Center, University of Notre Dame, 251 Nieuwland Hall, Notre Dame, IN 46556, United States.
Lambert
Timothy N
TN
Smith
Bradley D
BD
D020355:Cholates / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000378:metabolism*; D010718:Phosphatidylserines / Q000097:blood*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D016339:Spectrometry, Mass, Fast Atom Bombardment
D020355:Cholates; D008565:Membrane Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins