Prenatal alcohol exposure affects galactosyltransferase activity and glycoconjugates in the Golgi apparatus of fetal rat hepatocytes.
Prenatal exposure to alcohol affects the morphological, structural, and functional features of the Golgi apparatus (GA), thus altering the glycosylation process in fetal hepatocytes. To elucidate the cellular mechanisms underlying these alterations, we have studied the effect of alcohol exposure in utero on the activity of liver galactosyltransferase, an enzyme involved in the glycosylation process, and on the hepatic glycoprotein sugar composition. For this, livers from 21-day-old fetuses obtained from control and ethanol-fed rats were used. Galactosyltransferase (GT) activity was determined in isolated GA cis and trans fractions. Colloidal gold-labeled lectin cytochemistry was used to analyze sugar residues in hepatocytes at the subcellular level. Finally, the integrity of the GA after alcohol treatment was assessed by electron microscopy and by evaluating the distribution of the Golgi beta-COP, a protein involved in vesicular trafficking. Prenatal alcohol exposure induces a significant increase in both liver weight and total protein content in the trans Golgi. Moreover, this treatment decreases the activity of galactosyltransferase, increases alpha-L-Fuc residues, and reduces the number of alpha-Man, GlcNAc(beta1,4,GlcNAc)1,2, GalNAc alpha1,3GalNAc, alpha-GalNAc, and a-Gal residues. Alcohol exposure also causes the Golgi cisternae to disappear in about 30% of the hepatocytes, and reduces 75% the number of anti-Golgi beta-COP protein binding sites. Our results suggest that the decrease in galactosyltransferase activity, the alterations in the oligosaccharide chain composition, and the reduction in the amount of Golgi beta-COP protein could be involved in the alterations in the glycosylation process, as well as in the accumulation of hepatic proteins observed after prenatal alcohol exposure. These alterations could contribute, therefore, to the alcohol-induced injury in the developing liver.
Renau-Piqueras
J
J
Cell Biology and Pathology, Centro de Investigación, Hospital La Fe, Valencia, Spain.
Guasch
R
R
Azorín
I
I
Seguí
J M
JM
Guerri
C
C
D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D020756:Coatomer Protein; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005333:Fetus; D005700:Galactosyltransferases / Q000378:metabolism*; D006031:Glycosylation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D020756:Coatomer Protein; D008869:Microtubule-Associated Proteins; D000431:Ethanol; D005700:Galactosyltransferases