Alteration of protein glycosylation in liver diseases☆

Chronic liver diseases are a serious health problem worldwide. The current gold standard to assess structural liver damage is through a liver biopsy which has several disadvantages. A non-invasive, simple and non-expensive test to diagnose liver pathology would be highly desirable. Protein glycosylation has drawn the attention of many researchers in the search for an objective feature to achieve this goal. Glycosylation is a posttranslational modification of many secreted proteins and it has been known for decades that structural changes in the glycan structures of serum proteins are an indication for liver damage. The aim of this paper is to give an overview of this altered protein glycosylation in different etiologies of liver fibrosis / cirrhosis and hepatocellular carcinoma. Although individual liver diseases have their own specific markers, the same modifications seem to continuously reappear in all liver diseases: hyperfucosylation, increased branching and a bisecting N-acetylglucosamine. Analysis at mRNA and protein level of the corresponding glycosyltransferases confirm their altered status in liver pathology. The last part of this review deals with some recently developed glycomic techniques that could potentially be used in the diagnosis of liver pathology.

Abbreviations: ER, endoplasmic reticulum, Asn, asparagine, Ser, serine, Thr, threonine, GlcNAc, N-acetylglucosamine, HCC, hepatocellular carcinoma, ALD, alcoholic liver diseases, CDT, carbohydrate-deficient transferrin, ST6GalI, β-galactoside α2,6 sialyltransferase, TSA, total sialic acid, FSA, free sialic acid, Hp, haptoglobin, Con A, Concanavalin A, Apo E, Apolipoprotein E, GnT-III, N-acetylglucosaminyltransferase III, LAL, lysosomal acid lipase, HPLC, high performance liquid chromatography, MALDI-TOF, matrix assisted laser desorption/ionization time-of-flight, AGP, α1-acid glycoprotein, GnT-V, N-acetylglucosaminyltransferase V, HBx, HBV x-protein, α1-6 FT, α1-6 fucosyltransferase, LCA, lens culinaris agglutinin, E-PHA, Phaseolus vulgaris: erythroagglutinating, L-PHA, Phaseolus vulgaris: leuco-agglutinating, AAT, α-1-antitrypsin, TF, transferrin, DEN, diethylnitrosamine, DSA-FACE, DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis, IgG, immunoglobulin G

Keywords: Glycosylation, Liver fibrosis, Hepatocellular carcinoma, Glycomics, Bio-marker