Abstract
The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase is the key enzyme in sialic acid biosynthesis. Loss of UDP-GlcNAc 2-epimerase activity results in a hyposialylated phenotype as shown for two human hematopoietic cell lines that lack the specific mRNA. We found that treatment with the DNA methylation inhibitor 5'-aza-2'-deoxycytidine (5-aza-dC) restored the UDP-GlcNAc 2-epimerase/ManNAc kinase mRNA, as well as enzyme activity and cell surface sialylation. Increase of UDP-GlcNAc 2-epimerase activity by 5-aza-dC treatment was also found for a rat Morris hepatoma cell line. These results indicate a regulation of UDP-GlcNAc 2-epimerase/ManNAc kinase expression on the transcriptional level by DNA methylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carbohydrate Epimerases / metabolism*
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Carbohydrate Epimerases / physiology*
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Carcinoma, Hepatocellular / metabolism
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Cell Line
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Cell Membrane / metabolism
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DNA / metabolism
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DNA Methylation
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Flow Cytometry
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Humans
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Luciferases / metabolism
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Methylation
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N-Acetylneuraminic Acid / biosynthesis
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N-Acetylneuraminic Acid / metabolism
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Promoter Regions, Genetic
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RNA, Messenger / metabolism
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Rats
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
Substances
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DNA, Complementary
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RNA, Messenger
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DNA
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Luciferases
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Carbohydrate Epimerases
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UDP acetylglucosamine-2-epimerase
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N-Acetylneuraminic Acid