Liver Galβ1, 4GlcNAc a2, 6-sialyltransferase is Down-regulated in Human Alcoholics: Possible Cause for the Appearance of Asialoconjugates

Galβl, 4GlcNAc a2, 6-sialyltransferase (ST6GalI) mediates the glycosylation of proteins and lipids to form functionally important glycoproteins and glycolipids in the Golgi compartment. Our previous work demonstrated that chronic ethanol feeding in rats caused a marked 59% decrease of ST6GalI activity as well as ST6GalI mRNA level in the liver that were due to decreased stability of the mRNA. Clinical observations show that down-regulation of ST6GalI gene and consequent impaired activity of ST6GalI seems to be the major cause for the appearance of asialoconjugates in the blood of chronic alcoholics. The plasma carbohydrate-deficient transferrin (CDT) and sialic acid index of plasma apolipoprotein J (SIJ) were also altered in the alcoholic group compared to the non drinkers. We have now investigated how alcohol affects the gene regulation of ST6GalI and possible mechanism in post-mortem human liver specimens taken from non drinkers group, moderate-alcohol drinkers and heavy–alcohol drinkers. Real-time PCR analyses of the liver RNA extract showed that ST6GalI mRNA level was progressively decreased by 49% in moderate drinkers (p