Oxidative inactivation of paraoxonase - implications in diabetes mellitus and atherosclerosis

Sonia-Athina P Karabina, Alexander N Lehner, Elizabeth Frank, Sampath Parthasarathy, Nalini Santanam

Research output: Contribution to JournalArticlepeer-review

Abstract

Human serum paraoxonase (PON1) has been implicated to play an important role in cardiovascular disease and diabetes. Studies in the literature indicate that PON1 has two different enzyme activities, i.e., esterase and hydroperoxide reducing activities. The objective of this study was to establish the importance of these two activities and to distinguish between them. As the addition of copper immediately inactivated the enzyme, we used auto-oxidation as the model system. Auto-oxidation of HDL resulted in more than 80% reduction of the esterolytic activity, which was protected by antioxidants, Vitamin E (50%) and PDTC (95%) and completely by 1 M glucose. In contrast, the hydroperoxide reducing activity, using unesterified hydroperoxides remained unaffected with time. We also used pNPHPODE (novel substrate) to establish that hydrolysis might be a prerequisite for the enzyme to act on the esterified hydroperoxide. The results indicated that the hydrolysis of the substrate was inhibited under oxidizing conditions with no reduction of the hydroperoxide. Overall, our findings suggest that protecting the esterolytic activity of PON1 by antioxidants might be important in preserving its action on phospholipid peroxides and a concerted reaction involving the esterolytic and hydroperoxide reducing activities might be suggested for the action of PON1
Original languageEnglish
JournalBiochimica et Biophysica Acta (BBA) - General Subjects
Volume1725
Issue number2
DOIs
Publication statusPublished - 15 Sep 2005

Fingerprint

Dive into the research topics of 'Oxidative inactivation of paraoxonase - implications in diabetes mellitus and atherosclerosis'. Together they form a unique fingerprint.

Cite this