Effect of 3,4-dihydroxyphenylalanine on Cu(2+)-induced inactivation of HDL-associated paraoxonasel and oxidation of HDL; inactivation of paraoxonasel activity independent of HDL lipid oxidation

Su Duy Nguyen, Dai-Eun Sok
Free Radical Research 2004, 38 (9): 969-76
Paraoxonasel (PON1), one of HDL-asssociated antioxidant proteins, is known to be sensitive to oxidative stress. Here, the effect of endogenous reducing compounds on Cu(2+)-mediated inactivation of PON1 was examined. Cu(2+)-mediated inactivation of PON1 was enhanced remarkably by catecholamines, but not by uric acid or homocysteine. Furthermore, catecholamines such as 3,4-dihydroxyphenylalanine (DOPA), dopamine or norepinephrine were more effective than caffeic acid or pyrocatechol in promoting Cu(2+)-mediated inactivation of PON1, suggesting the importance of dihydroxybenzene group as well as amino group. DOPA at relatively low concentrations showed a concentration-dependent inactivation of PON1 in a concert with Cu2+, but not Fe2+. The DOPA/Cu(2+)-induced inactivation of PON1 was prevented by catalase, but not hydroxyl radical scavengers, consistent with Cu(2+)-catalyzed oxidation. A similar result was also observed when HDL-associated PON1 (HDL-PON1) was exposed to DOPA/Cu2+. Separately, it was found that DOPA at low concentrations (1-6 microM) acted as a pro-oxidant by enhancing Cu(2+)-induced oxidation of HDL, while it exhibited an antioxidant action at > or = 10 microM. In addition, Cu(2+)-oxidized HDL lost the antioxidant action against LDL oxidation. Meanwhile, the role of DOPA/Cu(2+)-oxidized HDL differed according to DOPA concentration; HDL oxidized with Cu2+ in the presence of DOPA (60 or 120 microM) maintained antioxidant activity of native HDL, in contrast to an adverse effect of DOPA at 3 or 6 microM. These data indicate that DOPA at micromolar level may act as a pro-oxidant in Cu(2+)-induced inactivation of PON1 as well as oxidation of HDL. Also, it is proposed that the oxidative inactivation of HDL-PON1 is independent of HDL oxidation.

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