Effects of Chronic Ethanol on Enzymes Regulating Sialylation and Desialylation of Transferrin in Rats

Abstract

Transferrin is N-glycosylated glycoprotein and plays an important role in iron transport from sites of absorption and storage to sites of utilization. Chronic ethanol alters the normal microheterogeneity pattern of transferrin as a consequence of changes in the sialic acid content. However the underlying basis of this change in sialic acid contents of transferrin in alcohol abuse remains unclear. We have undertaken this study in order to investigate the effects of chronic ethanol in rats with respect to the hepatic rate of (i) transferrin synthesis based on labeled leucine incorporation, (ii) the incorporation of labeled N-acetyl mannosamine (NAM) into sialic acid residues of transferrin, and (iii) roles of specific sialyltransferase and sialidase at hepatic subcellular level. The results showed no significant difference in the incorporation of labeled leucine into transferrin at all levels between the control and ethanol group, whereas the incorporation of NAM into transferrin was significantly decreased by 84% (p < 0.001) both at the whole cell and Golgi level. Thus, the incorporation of labeled NAM relative to the incorporation of labeled leucine into hepatic transferrin was significantly decreased by 86% (p < 0.001) in chronic ethanol-treated animals as compared with the controls both at the whole cell golgi levels. These data are further supported by our finding of concomitant decrease in the activity of beta-galactoside alpha 2,6-sialyltransferase by 58% (p < 0.01) in ethanol-treated rats as compared with control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol impairs monosaccharide uptake and glycosylation in cultured rat astrocytes

“…In addition, it has emerged as a key step of several developmental signal-transduction pathways (Fortini 2001). Chronic and acute alcohol exposure affects both the content and secretion of some glycoproteins as well as the nature of the complex glycoconjugates of many crucial glycoproteins (Ghosh et al 1993(Ghosh et al , 1998Rosenberg and Noble 1994;Arndt 2001). Indeed, the presence of altered glycoproteins, including the carbohydrate-deficient transferrin or CDT, has been reported in the serum of alcoholic patients with liver disease (Stibler 1991;Wang et al 1993;Arndt 2001).…”

“…H-ManNAc, the direct obligate metabolic precursor for NeuNAc) (Ghosh et al 1993;Pellerin and Magistretti 1994;Rosenberg and Noble 1994;Ghosh et al 1998).…”

Capillary electrophoresis and the clinical laboratory

“…Generalized disturbances in liver metabolism affect this steady-state, resulting in higher or lower degrees of glycosylation and sialylation. In particular, excessive alcohol ingestion seems to inhibit sialyltransferases, possibly through acetaldehyde [84] and glycosyltransferases [85,86] and stimulate cytosolic and plasma membrane sialydases [85][86][87] resulting in increased levels of asialo-, monosialo-, and disialo-Tf's. There is also evidence of depressed expression of the sialyltransferase genes [88], and reduced uptake through hepatocyte receptors [86].…”

Chronic ethanol consumption upregulates the cytosolic and plasma membrane sialidase genes, but downregulates lysosomal membrane sialidase gene in rat liver

“…The appearance of carbohydrate-deficient transferrin (CDT) in the plasma of chronic alcohol consumers has been established as a viable marker of chronic alcohol consumption [9,10]. Hepatic sialylations of transferrin, an N-glycosylated protein and apolipoprotein E, an O-glycosylated protein, are markedly impaired in ethanol-fed rats as compared to the pair-fed controls [11][12][13].…”

“…To define the significance and molecular mechanisms of aberrant sialylation in alcoholics, we have focused attention on sialidases and sialyltransferases [12], two of the key enzymes involved in the metabolism of glycoproteins and glycolipids. Sialyltransferases are glycosyltransferases which catalyze the transfer of sialic acid to the nonreducing terminal positions on the carbohydrate groups of glycoproteins and glycolipids in the Golgi compartment [14].…”