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Iron–ascorbic acid‐induced oxidant stress and its quenching by paraoxonase 1 in HDL and the liver: Comparison between humans and rats
Author(s) -
Trudel K.,
Sinnett D.,
James R.W.,
Delvin E.,
Amre D.,
Seidman E.,
Levy E.
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20542
Subject(s) - pon1 , lipid peroxidation , paraoxonase , microsome , chemistry , ascorbic acid , antioxidant , oxidative stress , biochemistry , butylated hydroxytoluene , lipoprotein , medicine , endocrinology , low density lipoprotein , enzyme , cholesterol , biology , food science , genotype , gene
Paraoxonase 1 (PON1) is a serum enzyme closely associated with high‐density lipoprotein (HDL), which may protect against atherosclerosis by hydrolyzing lipid peroxides and several organophosphorus compounds. The purpose of the present study was to test the hypothesis that lipid peroxidation modifies the activity and protein mass of PON1 in humans and rats. Our findings revealed that the bulk of the activity monitored by the hydrolysis of paraoxon and phenyl acetate was confined to liver intracellular endoplasmic reticulum‐derived microsomes and was mostly recovered in circulating HDL 3 . Confirmation was obtained by the determination of PON1 expression by Western blot. It is noteworthy that PON1 levels were consistently decreased in human sera, HDL, and liver microsomes compared with rat counterparts. Concomitant with iron‐ascorbate‐mediated lipid peroxidation, there was a decline in PON1 activity and protein in both HDL 3 and microsomes, which was attenuated by butylated hydroxytoluene antioxidant treatment. The current data indicate that PON1 localization in microsomes and HDL 3 could represent a selective cellular and lipoprotein response to oxidative stress. This was tested by the iron‐ascorbate oxygen‐radical generating system. It is also proposed that the increased PON1 level may have a function related to the well‐known atherosclerosis resistance of rats. © 2005 Wiley‐Liss, Inc.