title: Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on.
abstract: Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes several organophosphorus (OP) insecticides and nerve agents, a number of exogenous and endogenous lactones, and metabolizes toxic oxidized lipids of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility to OP toxicity, cardiovascular diseases and several other diseases. Serum PON1 activity in a given population can vary by at least 40-fold. Most of this variation can be accounted for by genetic polymorphisms in the coding region (Q192R, L55M) and in the promoter region (T-108C). However, exogenous factors may also modulate PON1 activity and/or level of expression. This paper examines various factors that have been found to positively modulate PON1. Certain drugs (e.g. hypolipemic and anti-diabetic compounds), dietary factors (antioxidants, polyphenols), and life-style factors (moderate alcohol consumption) appear to increase PON1 activity. Given the relevance of PON1 in protecting from certain environmental exposure and from cardiovascular and other diseases, there is a need for further mechanistic, animal, and clinical research in this area, and for consideration of possible alternative strategies for increasing the levels and activity of PON1.
authors.affiliation: Dept. of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Seattle, WA 98105, USA. lgcosta@u.washington.edu
authors.forename: Lucio G
authors.initials: LG
authors.lastname: Costa
authors.forename: Gennaro
authors.initials: G
authors.lastname: Giordano
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
mesh_terms: D000428:Alcohol Drinking; D000975:Antioxidants / Q000494:pharmacology; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D004032:Diet; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors; D020536:Enzyme Activators / Q000494:pharmacology*; D004950:Esterases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011110:Polymorphism, Genetic; D059808:Polyphenols
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D020536:Enzyme Activators; D005419:Flavonoids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010636:Phenols; D059808:Polyphenols; D004950:Esterases; D043303:Aryldialkylphosphatase