title: Surfactant lipid peroxidation damages surfactant protein A and inhibits interactions with phospholipid vesicles.
abstract: The goal of these studies was to examine the effect of lipid peroxidation (LPO) on the function of surfactant protein A (SP-A). First, the optimal dialysis conditions for quantitative removal of EDTA and redoxactive metals from reagents were established. Surfactant phospholipids were incubated with free radical generators in the absence or presence of the SP-A or with BSA as a control. We found that SP-A inhibited copper-initiated LPO to an extent similar to BSA (P < 0.05). Exposure of SP-A to LPO was associated with an increase in the level of SP-A-associated carbonyl moieties and a marked reduction in SP-A-mediated aggregation of liposomes. LPO initiated by an azo-compound also resulted in enhanced protein oxidation and markedly inhibited SP-A-mediated liposome aggregation. The kinetics of aggregation of auto-oxidized and nonoxidized liposomes by nonoxidized SP-A was similar, suggesting that SP-A has similar affinities for oxidized and nonoxidized lipids. Oxidative inactivation of SP-A did not occur upon direct incubation of the protein with malondialdehyde alone. We conclude that exposure of SP-A to LPO results in oxidative modification and functional inactivation of SP-A by phospholipid radicals.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Cincinnati School of Medicine, Cincinnati, OH 45267, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Kuzmenko
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: J P
authors.initials: JP
authors.lastname: Bridges
authors.forename: F X
authors.initials: FX
authors.lastname: McCormack
mesh_terms: D004492:Edetic Acid / Q000032:analysis; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010743:Phospholipids / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism*
chemical_list: D008081:Liposomes; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D004492:Edetic Acid