Protective action of CLA against oxidative inactivation of paraoxonase 1, an antioxidant enzyme.
The effect of CLA on paraoxonase 1 (PON1), one of the antioxidant proteins associated with HDL, was investigated for its protective action against oxidative inactivation as well as its stabilization activity. When cis-9 (c9),trans-11 (t11)-CLA and t10,c12-CLA were examined for their protective activity against ascorbate/Cu(2+)-induced inactivation of PON1 in the presence of Ca2+, two CLA isomers exhibited a remarkable protection (Emax, 71-74%) in a concentration-dependent manner (50% effective concentration, 3-4 microM), characterized by a saturation pattern. Such a protective action was also reproduced with oleic acid, but not linoleic acid. Rather, linoleic acid antagonized the protective action of CLA isomers in a noncompetitive fashion. Additionally, the two CLA isomers also protected PON1 from oxidative inactivation by H2O2 or cumene hydroperoxide. The concentration-dependent protective action of CLA against various oxidative inactivation systems suggests that the protective action of CLA isomers may be mediated through their selective binding to a specific binding site in a PON1 molecule. Separately, the inactivation of PON1 by p-hydroxymercuribenzoate (PHMB), a modifier of the cysteine residue, was also prevented by CLA isomers, suggesting the possible existence of the cysteine residue in the binding site of CLA. The c9,t11-CLA isomer seems to be somewhat more effective than t10,c12-CLA in protecting against the inactivation of PON1 by either peroxides or PHMB, in contrast to the similar efficacy of these two CLA isomers in preventing ascorbate/Cu(2+)-induced inactivation of PON1. Separately, CLA isomers successfully stabilized PON1, but not linoleic acid. These data suggest that the two CLA isomers may play a beneficial role in protecting PON1 from oxidative inactivation as well as in its stabilization.
Su
Nguyen-Duy
ND
College of Pharmacy, Chungnam National University, Taejon 305-764, Korea.
Liu
Xi-Wen
XW
Kim
Mee Ree
MR
Jeong
Tae-Sook
TS
Sok
Dai-Eun
DE
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D001555:Benzene Derivatives / Q000378:metabolism; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006902:Hydroxymercuribenzoates / Q000378:metabolism; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects
D000975:Antioxidants; D001555:Benzene Derivatives; D006902:Hydroxymercuribenzoates; D044243:Linoleic Acids, Conjugated; C030601:4-hydroxymercuribenzoate; D003300:Copper; D006861:Hydrogen Peroxide; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C007164:cumene hydroperoxide; D001205:Ascorbic Acid