PON1 paraoxonase activity is reduced during HDL oxidation and is an indicator of HDL antioxidant capacity.
The aim of this study was to investigate the effect of HDL oxidation on PON1 paraoxonase activity. Also, we were interested in investigating the mechanism by which PON1 could be inactivated and the correlation between its enzymatic activity and the antioxidant properties of HDL. Three different oxidation systems were used for the HDL oxidation: (1) oxidation induced by THP1 cells, (2) oxidation induced by copper ions at a concentration 10 microM, and (3) oxidation induced by *OH and O2.- oxygen free radicals produced by gamma-radiolysis. HDL oxidation was followed by the measurement of lipid peroxide formation, and PON1 activity was determined by measuring the rate of paraoxon hydrolysis. Our results show that HDL oxidation is accompanied by a reduction in the PON1 paraoxonase activity. The extent of PON1 inactivation depends both on the extent of HDL oxidation and on the oxidation system used. The rates of HDL oxidation and PON1 inactivation were significantly correlated (r = 0.93, p < 0.0054). Our results show that oxidized HDL loses its protective effect toward LDL oxidation. The antioxidant action of HDL towards LDL oxidation and the degradation of PON1 paraoxonase activity were significantly correlated (r = 0.95, p < 0.04).
Jaouad
Leila
L
Centre de Recherche sur le Vieillissement-IUGS, Université de Sherbrooke, Sherbrooke, Que., Canada J1H 4C4.
Milochevitch
Christelle
C
Khalil
Abdelouahed
A
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D043303:Aryldialkylphosphatase; D002460:Cell Line; D003300:Copper / Q000494:pharmacology; D004950:Esterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D017665:Hydroxyl Radical / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D013481:Superoxides / Q000494:pharmacology
D000975:Antioxidants; D008075:Lipoproteins, HDL; D013481:Superoxides; D017665:Hydroxyl Radical; D003300:Copper; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human