This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/5/1146    most recent ATVBAHA.107.141747v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deakin, S. Articles by James, R. W. Search for Related Content PubMed PubMed Citation Articles by Deakin, S. Articles by James, R. W.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1146.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

HDL Oxidation Compromises its Influence on Paraoxonase-1 Secretion and its Capacity to Modulate Enzyme Activity

Sara Deakin; Xenia Moren; Richard W. James

From the Clinical Diabetes Unit, Service of Endocrinology, Diabetes and Nutrition, University Hospital, 1211 Geneva 14, Switzerland.

Correspondence to Prof R.W. James, Clinical Diabetes Unit, Service of Endocrinology, Diabetes and Nutrition, University Hospital, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail Richard.James{at}hcuge.ch

Objective— The purpose of this study was to analyze the consequences of HDL oxidation for paraoxonase-1 metabolism and function.

Methods and 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.

Oxidation of HDL reduced its ability to promote paraoxonase-1 secretion and to improve the activity of the secreted enzyme. It was not related to modified affinity of HDL for the cell, or lipoperoxide-mediated enzyme inactivation. The degree of HDL oxidation was inversely correlated with the concentration of associated paraoxonase-1.

Key Words: HDL • oxidative stress • myeloperoxidase • hepatocyte • lactonase

This article has been cited by other articles:

				P. Jaichander, K. Selvarajan, M. Garelnabi, and S. Parthasarathy Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin J. Lipid Res., October 1, 2008; 49(10): 2142 - 2148. [Abstract] [Full Text] [PDF]

				X. Moren, S. Deakin, M.-L. Liu, M.-R. Taskinen, and R. W. James HDL subfraction distribution of paraoxonase-1 and its relevance to enzyme activity and resistance to oxidative stress J. Lipid Res., June 1, 2008; 49(6): 1246 - 1253. [Abstract] [Full Text] [PDF]

				M. Valiyaveettil, N. Kar, M. Z. Ashraf, T. V. Byzova, M. Febbraio, and E. A. Podrez Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Blood, February 15, 2008; 111(4): 1962 - 1971. [Abstract] [Full Text] [PDF]