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KMID : 0614020060210010011
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Journal of Pharmaceutical Sciences (C.N.U.)
2006 Volume.21 No. 1 p.11 ~ p.18
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Causes responsible for the in vivo reduction of activity of paraoxonase 1, a detoxifying enzyme of anticholinesterase organophosphates
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Sok Dai-Eun
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Abstract
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Paraoxonase 1(PON1), which is well known to hydrolyze organophosphates such as paraoxon and nerve agents, is widely distributed in blood, liver, heart, kidney as well as brain. Also, mRNA for PON1 was detected in a number of tissues apart from the liver, suggesting a possible role for this protein family. Initial investigation of PON1 focused on its ability to hydrolyze organophosphate compounds, playing a major role in the detoxification of these compounds. Recent interest in the enzyme has arisen from the observations that they possess antioxidant action against copper ion-catalyzed oxidation of lipids or proteins. Such an antioxidant action could contribute to further augment the benefit of paraoxonase1 in preventing against organophosphate poisoning, especially accompanied by oxidative stress. Therefore, it is important to maintain PON1 activity in vivo. Above all, it has been of a curiosity to find the causes responsible for the loss of PON1 activity, and provide the measures to prevent against the reduction of PON1 level. The mechanisms responsible for the in vivo inactivation of PON1 by oxidative conditions will be reviewed. In addition, the inhibition of PON1 activity by endogenous factors including negatively-charged lipids will be addressed. Further, the strategy to preserve the activity of paraoxonase 1, a detoxifier of anticholinesterase organophosphates, in vivo system will be discussed. Finally, there will be a discussion on the possible common function of two hydrolases, acetylcholinesterase and paraoxonase 1, in preventing oxidative stress.
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KEYWORD
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PON1, inhibition, oxidative inactivation, fatty acid, lysophospholipids, negatively-charged lipids
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