Liver α2,6‐sialylation by ST6Gal‐1: Ablation of the hepatic promoter alters the α2,6‐sialylation pattern of serum glycoproteins but not the overall degree of sialylation

Abstract

The sialyltransferase ST6Gal‐1, which mediates the synthesis of the α2,6‐sialyl linkage to Gal( ?1,4)GlcNAc, is expressed ubiquitously but with particular abundance in the liver. The acute phase response, the liver's response to insult or injury, results in addition of heavily sialylated proteins into circulation. The acute phase response is also accompanied by hepatic up‐regulation of ST6Gal‐1 expression, but the functional relevance of hepatic ST6Gal‐1 remains unclear.Previously, we generated a mutant mouse, Siat1ΔP1, by inactivation of the P1 region in the liver of the ST6Gal‐1 gene. Past experiments have shown myelopoetic disruption involving altered sialylation of serum glycoproteins. Initial examination demonstrated an essential unchanged degree of overall sialylation between wild‐type and δP1 animals, and serum glycoproteins in animals with globally inactivated ST6Gal‐1 remain fully sialylated. We use 2D gel electrophoresis, lectin affinity, and silver staining for analysis of serum glycoproteins to reveal significant qualitative and quantitative changes in the sialylation of serum glycoproteins between genotypes. These changes were further magnified after subcutaneous exposure of the animals to turpentine. We pay special attention to these mouse models at three crucial time points. Thus, the extent and types of sialyl linkages on serum glycoproteins are important.