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KMID : 0614020030180010032
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Journal of Pharmaceutical Sciences (C.N.U.)
2003 Volume.18 No. 1 p.32 ~ p.36
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Prevention Against Cumene Hydroperoxide-mediated Oxidative Inactivation of Paraoxonase 1
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Nguyen Duy-Su
Liu Xi-Wen
Kim Ju-Ryung
Sok Dai-Eun
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Abstract
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Paraoxonase 1 (PON1), an enzyme associated with high density lipoprotein (HDL), is known to protect low density lipoprotein (LDL) from lipid peroxidation involving copper ion. However, Paraoxonase 1 activity was observed to decrease during LDL oxidation. Here, the inactivation of PON1 by various peroxides was examined. Paraoxonase 1, purified from human plasma, was subjected to cumene hydroperoxide, hydrogen peroxide or tert-butyl hydroperoxide. PON activity, based on the hydrolysis of phenyl acetate, decreased by approximately 40 and 38 %, respectively, after the exposure to 2mM cumene hydroperoxide and hydrogen peroxide, while tert-butyl hydroperoxide had no remarkable inhibitory effect. Next, the compounds capable of preventing against cumene hydroperoxide-induced inactivation of PONl were screened. While quercetin or phenyl acetate failed to protect PON1, lauric acid or calcium chloride was found to protect PONl from cumene hydroperoxide-induced inactivation. Especially, lauric acid appeared to show the greater protection than the other fatty acids tested. In further study, lauric acid showed a dose-dependent protection with an E& value of around 35 μM. Based on these results, It is proposed that the alky hydroperoxide-induced inactivation of Paraoxonase 1 can be prevented by a proper fatty acid recipe.
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KEYWORD
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Paraoxonase, cumene hydroperoxide, Inactivation, Protection
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