Search resultsLight, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans
Title
Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans
Publication type
Journal Article
Year of Publication
2003
Authors
Journal
Metabolism: Clinical and Experimental
Volume
52
Issue
10
Pagination
1287 - 1294
Date published
2003
ISBN
00260495 (ISSN)
Keywords
Adult, alcohol, Alcohol Drinking, alcoholic beverage, Animal, animal experiment, Animals, article, aryldialkylphosphatase, blood, cardiotonic agent, Cardiotonic Agents, clinical article, comparative study, controlled study, down regulation, Down-Regulation, drinking behavior, drug effect, enzyme activation, enzyme activity, enzyme polymorphism, enzymology, esterase, Esterases, Ethanol, feeding, genetic polymorphism, genetics, Heterozygote, high density lipoprotein, Homozygote, human, human experiment, Humans, lipoprotein blood level, Lipoproteins, LDL, Liver, liver level, low density lipoprotein, macrophage, male, messenger RNA, metabolism, Middle Aged, nonhuman, normal human, oxidation reduction reaction, Oxidation-Reduction, phenotype, Polymorphism, Genetic, PON1 protein, human, priority journal, protein blood level, protein expression, protein transport, rat, Rats, Rats, Wistar, RNA, Messenger, upregulation, Wistar rat
Abstract
Paraoxonase 1 (PON) may contribute to the cardioprotective action of high-density lipoprotein (HDL) because it inhibits low-density lipoprotein (LDL) oxidation, a prerequisite for the onset of atherosclerosis. Because light drinking and heavy drinking have diametrically opposite effects on cardioprotection, we have determined the effects of ethanol dosage on rat serum PON activity and its hepatic expression. Furthermore, we have investigated PON activity and polymorphism in human light and heavy drinkers. Our results confirm that HDL-PON inhibited LDL oxidation, destroyed oxidized LDL, and inhibited its uptake by macrophages. Light ethanol feeding caused a 20% to 25% (P < .05) increase in PON activity in both serum and liver and a 59% (P < .001) increase in the level of liver PON mRNA compared with pair-fed control rats. In contrast, heavy ethanol feeding caused a 25% (P < .05) decrease in serum and liver PON activities with a 51% (P < .01) decrease in liver PON mRNA level. Light drinkers had a 395% (P < .001) higher, whereas heavy drinkers had a 45% (P < .001) lower serum PON activity compared with nondrinkers. Significantly, the number of homozygotes versus heterozygotes with respect to high or low activity PON phenotype was similar in all the groups. Therefore, we conclude that light drinking upregulates, whereas heavy drinking downregulates PON activity and its expression, irrespective of its genetic polymorphism.