S-glutathionylation Regulates Hdl-associated Paraoxonase 1 (Pon1) Activity.
From: The Lipid Research Laboratory, The Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, 31096 Haifa, Israel.
Biochemical and biophysical research communications
- Publish Date: Dec 2006
- ISSN: 0006-291X
- Volume: 351
- Issue: 2
- Pages: 492-8
- Medium: Print
- Language: English
- Citation (JAMA): Rozenberg Orit, Aviram Michael, et al. S-glutathionylation Regulates Hdl-associated Paraoxonase 1 (Pon1) Activity.. Biochem. Biophys. Res. Commun. Dec 2006;351:492-8
Abstract
HDL-associated paraoxonase 1 (PON1) undergoes inactivation under oxidative stress and is preserved by dietary antioxidants. PON1 cysteines can affect PON1 enzymatic activities. S-Glutathionylation, a redox regulatory mechanism characterized by the formation of a mixed disulfide between a protein thiol and oxidized glutathione (GSSG), was shown to preserve some enzymes from irreversible inactivation under pathological conditions. We questioned whether PON1 activity is regulated by S-glutathionylation. Incubation of PON1 or HDL with GSSG indeed resulted in a dose-dependent inactivation of PON1 activities, including its physiological activity to increase HDL-mediated macrophage cholesterol efflux. This PON1 inactivation was associated with the formation of a mixed disulfide bond between GSSG and PON1’s cysteine residue(s), as detected by immunoblotting with anti-glutathione IgG. PON1 activity was recovered following the addition of a reducing agent, DL-Dithiothreitol (DTT), to the PON1-SSG complex. We thus conclude that HDL-associated serum PON1 can undergo S-glutathionylation under oxidative stress with a consequent reversible inactivation.
Mesh Headings (Keywords): Animals, Aryldialkylphosphatase, Cell Line, Cholesterol, Cysteine, Dithiothreitol, Enzyme Activation, Glutathione, Glutathione Disulfide, Lipoproteins, HDL, Macrophages, Mice, Oxidation-Reduction, Reducing Agents
Check for Full Text / PubMed Unique Identifier (PMID): 17070779
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