Mechanism of α-Cyclodextrin-lnduced Hemolysis. 1. The Two-Step Extraction of Phosphatidylinositol from the Membrane

Abstract

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.

A Moderate Interaction of Maltosyl-α-cyclodextrin with Caco-2 Cells in Comparison with the Parent Cyclodextrin

“…In addition, a-CyD is reported to interact with phosphatidylinositol strongly, but not phosphatidylcholine. 26,27) Furthermore, Miyajima et al 28) and Nishijo et al 29) reported that a-CyD sequesters DPPC molecules from the liposomes and forms an inclusion complex with DPPC out of a membrane matrix. Thus, the mode of the interactions between a-CyD and G 2 -a-CyD and lipids in the biological membranes seems to be complicated.…”

Pharmacokinetics, Efficacy, and Safety Evaluation of Docetaxel/Hydroxypropyl-Sulfobutyl-β-Cyclodextrin Inclusion Complex

“…CDs have been reported to interact with cell membrane constituents such as cholesterol, phospholipids, and phosphatidylinositols, resulting in the induction of hemolysis of RBC (25)(26)(27)(28). The magnitude of the hemolytic activity of the parent CDs is reported to increase in the order of γ-CD<α-CD<β-CD (25).…”

Cyclodextrins enhance recombinant phosphatidylinositol phosphate kinase activity

“…Cyclodextrins are also used in the cosmetics industry to create longer lasting fragrances and prevent the oxidation and degradation of oils (5). Laboratory applications include using cyclodextrins as size-exclusion columns, as artificial chaperones to remove detergents and facilitate the refolding of recombinant proteins (7,8), as a vehicle to develop molecular machines (9), and as a means for the delivery and removal of lipids from membranes to study bilayers and lipid rafts (10-13).We have taken advantage of the ability of cyclodextrins to bind lipids (11,12,14) and deliver them to cells (13) and asked whether cyclodextrin could be used to deliver inositol phospholipids to recombinant lipid kinases for in Abbreviations: At PIPK1, Arabidopsis thaliana phosphatidylinositol phosphate kinase 1; ␣ CD, ␤ CD, and ␥ CD, ␣ -, ␤ -, and ␥ -cyclodextrin; GST, glutathione-S -transferase; NBD-PtdInsP, d ( ϩ )-sn -1-O -[1- [6 Ј -[6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl) …”

“…We have taken advantage of the ability of cyclodextrins to bind lipids (11,12,14) and deliver them to cells (13) and asked whether cyclodextrin could be used to deliver inositol phospholipids to recombinant lipid kinases for in Abbreviations: At PIPK1, Arabidopsis thaliana phosphatidylinositol phosphate kinase 1; ␣ CD, ␤ CD, and ␥ CD, ␣ -, ␤ -, and ␥ -cyclodextrin; GST, glutathione-S -transferase; NBD-PtdInsP, d ( ϩ )-sn -1-O -[1- [6 Ј -[6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl) …”

“…We have taken advantage of the ability of cyclodextrins to bind lipids (11,12,14) and deliver them to cells (13) and asked whether cyclodextrin could be used to deliver inositol phospholipids to recombinant lipid kinases for in vitro lipid kinase assays. We found that using cyclodextrin for substrate delivery increased At PIPK1 specific activity 4-to 6-fold compared with sonicated substrate alone or Triton-mixed micelles, respectively.…”