title: Sphingosine induces the aggregation of imine-containing peroxidized vesicles.
abstract: Lipid peroxidation plays a central role in the pathogenesis of many diseases like atherosclerosis and multiple sclerosis. We have analyzed the interaction of sphingosine with peroxidized bilayers in model membranes. Cu(2+) induced peroxidation was checked following UV absorbance at 245nm, and also using the novel Avanti snoopers®. Mass spectrometry confirms the oxidation of phospholipid unsaturated chains. Our results show that sphingosine causes aggregation of Cu(2+)-peroxidized vesicles. We observed that aggregation is facilitated by the presence of negatively-charged phospholipids in the membrane, and inhibited by anti-oxidants e.g. BHT. Interestingly, long-chain alkylamines (C18, C16) but not their short-chain analogues (C10, C6, C1) can substitute sphingosine as promoters of vesicle aggregation. Furthermore, sphinganine but not sphingosine-1-phosphate can mimic this effect. Formation of imines in the membrane upon peroxidation was detected by (1)H-NMR and it appeared to be necessary for the aggregation effect. (31)P-NMR spectroscopy reveals that sphingosine facilitates formation of non-lamellar phase in parallel with vesicle aggregation. The data might suggest a role for sphingosine in the pathogenesis of atherosclerosis.
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain.
authors.forename: Noemi
authors.initials: N
authors.lastname: Jiménez-Rojo
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Viguera
authors.affiliation: Servicio General de Resonancia Magnética Nuclear, Universidad del País Vasco, Bilbao, Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Collado
authors.affiliation: Avanti Polar Lipids, Inc., Alabaster, AL 35214, USA.
authors.forename: Kacee H
authors.initials: KH
authors.lastname: Sims
authors.affiliation: Avanti Polar Lipids, Inc., Alabaster, AL 35214, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Constance
authors.affiliation: Avanti Polar Lipids, Inc., Alabaster, AL 35214, USA.
authors.forename: Kasey
authors.initials: K
authors.lastname: Hill
authors.affiliation: Avanti Polar Lipids, Inc., Alabaster, AL 35214, USA.
authors.forename: Walt A
authors.initials: WA
authors.lastname: Shaw
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain.
authors.forename: Félix M
authors.initials: FM
authors.lastname: Goñi
authors.affiliation: Unidad de Biofísica (CSIC, UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, P.O. Box 644, 48080 Bilbao, Spain. Electronic address: alicia.alonso@ehu.es.
authors.forename: Alicia
authors.initials: A
authors.lastname: Alonso
mesh_terms: D003300:Copper / Q000494:pharmacology; D007097:Imines / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D015227:Lipid Peroxidation; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013110:Sphingosine / Q000378:metabolism*
chemical_list: D007097:Imines; D008051:Lipid Bilayers; D008081:Liposomes; D003300:Copper; D013110:Sphingosine
keywords: Imine; Lipid peroxidation; Sphingosine; Vesicle aggregation