Su Nguyen-Duy, Liu Xi-Wen, Kim Mee Ree, Jeong Tae-Sook, Sok Dai-Eun
College of Pharmacy, Chungnam National University, Taejon 305-764, Korea.
Lipids. 2003 Jun;38(6):615-22. doi: 10.1007/s11745-003-1106-9.
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.
研究了共轭亚油酸（CLA）对对氧磷酶1（PON1）的影响，PON1是一种与高密度脂蛋白相关的抗氧化蛋白，考察了CLA对其抗氧化失活的保护作用及其稳定活性。当在Ca2+存在的情况下，检测顺-9（c9），反-11（t11）-CLA和反-10，顺-12-CLA对抗坏血酸/Cu(2+)诱导的PON1失活的保护活性时，两种CLA异构体呈现出显著的保护作用（最大效应值，71 - 74%），呈浓度依赖性（半数有效浓度，3 - 4 microM），具有饱和模式特征。油酸也能重现这种保护作用，但亚油酸不能。相反，亚油酸以非竞争性方式拮抗CLA异构体的保护作用。此外，这两种CLA异构体还能保护PON1免受过氧化氢或氢过氧化异丙苯的氧化失活。CLA对各种氧化失活系统的浓度依赖性保护作用表明，CLA异构体的保护作用可能是通过它们与PON1分子中特定结合位点的选择性结合来介导的。另外，CLA异构体也能防止半胱氨酸残基修饰剂对羟基汞苯甲酸（PHMB）导致的PON1失活，这表明CLA结合位点可能存在半胱氨酸残基。与这两种CLA异构体在防止抗坏血酸/Cu(2+)诱导的PON1失活中效果相似相比，c9，t11-CLA异构体在保护PON1免受过氧化物或PHMB失活方面似乎比反-10，顺-12-CLA稍微更有效。另外，CLA异构体成功地稳定了PON1，但亚油酸不能。这些数据表明，这两种CLA异构体在保护PON1免受过氧化失活及其稳定方面可能发挥有益作用。
