title: HDL oxidation compromises its influence on paraoxonase-1 secretion and its capacity to modulate enzyme activity.
abstract: OBJECTIVE
  The purpose of this study was to analyze the consequences of HDL oxidation for paraoxonase-1 metabolism and function.
  
  
  RESULTS
  HDL was oxidized with AAPH, copper ions, and hypochlorite. Secretion studies were performed using human paraoxonase-1-transfected cells lines and primary rat hepatocytes. Stability studies were performed with recombinant paraoxonase. Conditioned medium had significantly reduced paraoxonase-1 when Cu or AAPH-oxidized HDL was the acceptor complex (P<0.01); reduction was dose-dependent on the degree of oxidation. Oxidized HDL had a reduced capacity to stabilize/improve activity of secreted paraoxonase-1. Reduced secretion could not be attributed to enzyme inactivation by lipoperoxides, reduced binding affinity of HDL, or oxidation of the lipid component alone. Hypochlorite oxidation of HDL did not modify HDL-mediated paraoxonase-1 release, but activity of HDL-associated paraoxonase-1 was particularly sensitive to such treatment.
  
  
  CONCLUSIONS
  AAPH and copper, but not hypochlorite, oxidation of HDL compromises its ability to promote release of paraoxonase-1 and stabilize enzyme activity. HDL-associated paraoxonase-1 is highly sensitive to hypochlorite. Reducing paraoxonase-1 renders HDL susceptible to oxidation, which may compromise HDL function. It provides a novel example at the HDL level of the detrimental effects of oxidative stress, and underlines the need for further evaluation of the consequences of HDL oxidation.
authors.affiliation: Clinical Diabetes Unit, Service of Endocrinology, Diabetes and Nutrition, University Hospital, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Deakin
authors.forename: Xenia
authors.initials: X
authors.lastname: Moren
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000008:administration & dosage / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D008076:Cholesterol, HDL; D016877:Oxidants; D011994:Recombinant Proteins; D006997:Hypochlorous Acid; D043303:Aryldialkylphosphatase