Mechanism of alpha-cyclodextrin-induced hemolysis. 1. The two-step extraction of phosphatidylinositol from the membrane.
It has been suggested that the interaction of cyclodextrins with the lipid components of the erythrocyte membranes is the determining factor in the hemolysis induced by these cyclic oligosaccharides. In the case of alpha-cyclodextrin (cyclomaltohexose), phospholipids have been identified as the cell target. In our study, evidence for the interaction between alpha-cyclodextrin and different phospholipids has been obtained using synthetic membranes. Since phosphatidylinositol (PI) showed the strongest affinity for alpha-cyclodextrin, it has been selected to investigate the respective contributions of the polar head group and the aliphatic chains to the association process using 31P, 2H, and 1H NMR spectroscopy. In this work, we describe the two-step extraction of PI from the membrane following its association with alphaCD: a cyclodextrin molecule is first attracted to the membrane surface by electrostatic remote interactions and associates with the lipid head group. Then the whole PI molecule is extracted, and inclusion of its unsaturated sn-2 acyl chain into another alphaCD molecule occurs in the bulk.
Fauvelle
F
F
CRSSA, Unité de Biophysique, La Tronche, France.
Debouzy
J C
JC
Crouzy
S
S
Göschl
M
M
Chapron
Y
Y
D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D047391:alpha-Cyclodextrins; C032613:alpha-cyclodextrin