Increased expression of the selectin ligand sialyl-Lewis(x) by biochemical engineering of sialic acids |
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Authors: | Horstkorte Rüdiger Rau Kirstin Reutter Werner Nöhring Sabine Lucka Lothar |
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Institution: | Institut für Molekularbiologie und Biochemie, Charité-Universit?tsmedizin Berlin, 14195 Berlin-Dahlem, Germany. ruediger.horstkorte@medizin.fu-berlin.de |
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Abstract: | Sialylation of glycoproteins and glycolipids plays an important role during development, regeneration and pathogenesis of several diseases. The precursor of all physiological sialic acids is N-acetyl-d-mannosamine. Using N-propanoyl mannosamine, a novel precursor of sialic acid, we showed earlier that sialic acids with a prolonged N-acyl side chain (e.g., N-propanoyl neuraminic acid) are incorporated into cell surface glycoconjugates. In this study, we report the structural and functional consequences of the incorporation of the nonphysiological sialic acid, N-propanoyl neuraminic acid, into glycoconjugates of HL60-I cells. These cells do not express UDP-GlcAc-2-epimerase, the key enzyme of the biosynthesis of N-acetyl-d-mannosamine. Therefore, they do not express sialyl-Lewis(x) structures and consequently do not bind to selectins. Application of N-acetyl-d-mannosamine leads to the expression of sialyl-Lewis(x) structures and to binding to selectins. Surprisingly, incorporation of N-propanoyl neuraminic acid into glycoconjugates of these cells leads to a dramatic increase of sialyl-Lewis(x) structures and to increased adhesion to selectins. |
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Keywords: | Cell adhesion Selectins Carbohydrate ligands sialyl– Lewisx Sialic acid |
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