Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization.
The effect of lipids on PON1 (paraoxonase 1), one of antioxidant proteins in high-density lipoprotein, was investigated in respect to inhibition, protection against oxidative inactivation, and stabilization. When the effect of lipids on the PON1 activity was examined, a remarkable inhibition was expressed by polyenoic fatty acids (C18:2-C20:5). Linoleic acid, the most potent ( K(i), 3.8 microM), showed competitive inhibition. Next, various lipids were examined for prevention against the inactivation of PON1 by ascorbate/Cu2+, which caused a remarkable (>or =90%) inactivation of PON1. Compared with saturated fatty acids (C6-C18), exhibiting a modest protection (9-40%), monoenoic acids (C16:1-C20:1) showed a greater maximal protective effect (Emax, 70-82%), with oleic acid being the most effective (EC50, 2.7 microM). In contrast, polyenoic acids showed no protection. Noteworthy, linoleic acid prohibited the protective action of oleic acid non-competitively. In the structure-activity relationship, a negatively charged group seems to be required for the protective action. Consistent with this, dioleoylphosphatidylglycerol, negatively charged, was more protective than dioleoylphosphatidylcholine. These data, together with requirement of Ca2+ (EC50, 0.6 microM) for the protective action, may support the existence of a specific site responsible for the protective action. A similar protective action of lipids was also observed in the inactivation of PON1 by ascorbate/Fe2+, peroxides or p -hydroxymercuribenzoate. Separately, PON1 was stabilized by oleic acid or oleoylated phospholipids, in combination with Ca2+, but not linoleic acid. These results suggest that in contrast to an adverse action of linoleic acid, monoenoic acids or their phospholipid derivatives play a beneficial role in protecting PON1 from oxidative inactivation as well as in stabilizing PON1.
Nguyen
Su Duy
SD
College of Pharmacy, Chungnam National University, Gung-Dong, Yuseong-Ku, Taejon 305-764, South Korea.
Sok
Dai-Eun
DE
D043303:Aryldialkylphosphatase / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004795:Enzyme Stability / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D006902:Hydroxymercuribenzoates / Q000494:pharmacology; D007700:Kinetics; D019301:Oleic Acid / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology
D005227:Fatty Acids; D006902:Hydroxymercuribenzoates; D016877:Oxidants; D010743:Phospholipids; D011480:Protease Inhibitors; C030601:4-hydroxymercuribenzoate; D019301:Oleic Acid; D003300:Copper; D043303:Aryldialkylphosphatase; D001205:Ascorbic Acid