Epigenetically mediated loss of UDP-GlcNAc 2-epimerase/ManNAc kinase expression in hyposialylated cell lines.

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.

• Authors: Cornelia Oetke, Stephan Hinderlich, Werner Reutter, Michael Pawlita
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 308 Issue 4 Pg. 892-8 (Sep 05 2003) ISSN: 0006-291X [Print] United States
• PMID: 12927803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• RNA, Messenger
• DNA
• Luciferases
• Carbohydrate Epimerases
• UDP acetylglucosamine-2-epimerase
• N-Acetylneuraminic Acid

Topics

• Animals
• Carbohydrate Epimerases (metabolism, physiology)
• Carcinoma, Hepatocellular (metabolism)
• Cell Line
• Cell Membrane (metabolism)
• DNA (metabolism)
• DNA Methylation
• DNA, Complementary (metabolism)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Luciferases (metabolism)
• Methylation
• N-Acetylneuraminic Acid (biosynthesis, metabolism)
• Promoter Regions, Genetic
• RNA, Messenger (metabolism)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured