Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans.
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.
Rao
Manjunath N
MN
Lipid Research Laboratory and Gastrointestinal and Hepatology Section, Veterans Affairs Medical Center, Washington DC 20422, USA.
Marmillot
Philippe
P
Gong
Maoka
M
Palmer
David A
DA
Seeff
Leonard B
LB
Strader
Doris B
DB
Lakshman
M Raj
MR
D000328:Adult; D000428:Alcohol Drinking / Q000097:blood / Q000378:metabolism*; D000818:Animals; D043303:Aryldialkylphosphatase; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004950:Esterases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D000431:Ethanol; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human