Chronic ethanol consumption leads to destabilization of rat liver beta-galactoside alpha2,6-sialyltransferase mRNA.
Chronic ethanol consumption in rats is accompanied by decreased levels of Gal beta1,4GlcNAc alpha2,6-sialyltransferase (2,6-ST) activity in the liver. Our previous studies have shown that there is a concomitant decrease in the levels of 2,6-ST mRNA. In this study, the alteration in the regulation of 2,6-ST expression by chronic ethanol consumption was assessed by Northern hybridization, nuclear run-on experiments, and 2,6-ST mRNA stability studies. 2,6-ST downregulation was found at 4 weeks of feeding an ethanol diet (36% of calories from ethanol) and remained up to 8 weeks. The decrease in 2,6-ST mRNA levels was found to be dose-dependent, with lower dose of ethanol (12% and 24% of total dietary calories from ethanol) being ineffective and the effects being manifested only when 36% of the dietary calories were from ethanol. The effects of chronic ethanol feeding could be completely reversed within 1 week after ethanol consumption was stopped, when 2,6-ST mRNA levels were restored to normal. The downregulation was not sensitive to actinomycin D, indicating that the regulation was not affected at the transcriptional level but at the posttranscriptional level. This was confirmed by nuclear run-on experiments showing that the rate of 2,6-ST mRNA transcription was unaffected by ethanol. Finally, mRNA stability experiments showed that the half-life of 2,6-ST mRNA was reduced 50% in ethanol-fed rat livers compared with control rat livers. Taken together, the results show that 2,6-ST mRNA is regulated at the posttranscriptional level and chronic ethanol intake downregulates 2,6-ST expression by destabilizing its mRNA.
Rao
M N
MN
Lipid Research Laboratory, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
Lakshman
M R
MR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012799:Sialyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D012333:RNA, Messenger; D000431:Ethanol; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase