Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 308, Issue 4, Pages 892-898Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0006-291X(03)01471-2
Keywords
sialic acid; UDP-GlcNAc 2-epimerase/ManNAc kinase; DNA methylation; Morris hepatoma; gene silencing
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The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase is the key enzyme in sialic acid biosynthesis. Loss of UDPGlcNAc 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 UDPGlcNAc 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. (C) 2003 Elsevier Inc. All rights reserved.
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