Abstract
To determine the causes responsible for a preferential decrease of paraoxonase activity, which has been observed in the serum of patients with cardiovascular diseases, the inactivation or inhibition of paraoxonase 1 (PON1) by various endogenous factors was examined using paraoxon or phenyl acetate as a substrate. When purified PON1 was incubated with various endogenous oxidants or aldehydes, they failed to cause a preferential reduction of paraoxonase activity, suggesting no participation of the inactivation mechanism in the preferential loss of paraoxonase activity. Next, when we examined the inhibition of PON1 activity by endogenous lipids, monoenoic acids such as palmitoleic acid or oleic acid inhibited paraoxonase activity preferentially, in contrast to a parallel inhibition of both activities by polyunsaturated or saturated acids. Noteworthy, oleoylglycine inhibited paraoxonase activity, but not arylesterase activity, complying with the selective inhibition of paraoxonase activity. Moreover, such a selective inhibition of paraoxonase activity was also expressed by lysophosphatidylglycerol or lysophosphatidylinositol, but not by lysophosphatidylserine or lysophosphatidylcholine, indicating the importance of the type of head group. Furthermore, such a preferential or selective inhibition of paraoxonase activity was also observed with PON1 associated with HDL or plasma. These data suggest that some negatively charged lipids may correspond to factors causing the preferential inhibition of paraoxonase activity of PON1.
Highlights
To determine the causes responsible for a preferential decrease of paraoxonase activity, which has been observed in the serum of patients with cardiovascular diseases, the inactivation or inhibition of paraoxonase 1 (PON1) by various endogenous factors was examined using paraoxon or phenyl acetate as a substrate
To determine whether the oxidative inactivation of Paraoxonase 1 (PON1) may be responsible for the preferential reduction of paraoxonase activity, PON1 was exposed to various endogenous oxidants in 10 mM PBS buffer containing 1 mM Ca2ϩ, and the remaining activity was determined using paraoxon or phenyl acetate as a substrate
When PON1 was exposed to H2O2 or NaOCl, it was found that paraoxonase activity was less sensitive to NaOCl than was arylesterase activity, whereas H2O2 inactivated both activities to a similar extent (Table 1)
Summary
To determine the causes responsible for a preferential decrease of paraoxonase activity, which has been observed in the serum of patients with cardiovascular diseases, the inactivation or inhibition of paraoxonase 1 (PON1) by various endogenous factors was examined using paraoxon or phenyl acetate as a substrate. PON1 (1 arylesterase unit/ml) was incubated with phenyl acetate or paraoxon in the presence of two different lipids in 0.5 ml of 50 mM Tris buffer (pH 7.4) containing 1 mM Ca2ϩ at 25ЊC, and the formation of product was monitored as described above.
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