Lipid hydroperoxides permit deformation-dependent leak of monovalent cation from erythrocytes

T. Sugihara, W. Rawicz, E. A. Evans, R. P. Hebbel

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Subtle peroxidative perturbation of normal red blood cells (RBC) using t-butylhydroperoxide creates a leak pathway for monovalent cations that is reversibly activated by cell deformation. To determine what factor promotes expression of this unique membrane defect, we have dissected ''peroxidation'' into components that can be evaluated separately by comparing K leak from suitably modified RBC during elliptical deformation and parallel control incubation. Selective introduction of phospholipid hydroperoxides into normal RBC membranes successfully induces a deformation-dependent leak pathway having the same phenomenology as that previously documented for cells treated with t-butylhydroperoxide itself (fully recoverable; calcium-independent; inhibited at lower pH; K efflux balanced by Na influx). This leak pathway occurs in the absence of detectable secondary peroxidative change and appears to reflect a direct influence of lipid hydroperoxide. Using micropipette examination of vesicular bilayers reconstituted from RBC lipid extracts, we find that lipid from peroxidized RBC exhibits only a slight tendency to be less cohesive than normal lipid, apparently precluding isolated lipid properties as an explanation for altered permeability barrier function. However, addition of a hydrophobic membrane-spanning peptide to these same lipids significantly diminishes bilayer cohesion, an effect that is exacerbated further by the presence of peroxidized lipid. These observations suggest that lipid hydroperoxide is a necessary, but perhaps not sufficient, factor for induction of this unique leak pathway. Our results may be relevant to the abnormal cation homeostasis of sickle RBC in which deformation of an oxidatively perturbed membrane occurs during the sickling phenomenon.

Original languageEnglish (US)
Pages (from-to)2757-2763
Number of pages7
JournalBlood
Volume77
Issue number12
DOIs
StatePublished - 1991
Externally publishedYes

Fingerprint Dive into the research topics of 'Lipid hydroperoxides permit deformation-dependent leak of monovalent cation from erythrocytes'. Together they form a unique fingerprint.

Cite this