Polysialic acid bioengineering of neuronal cells by N-acyl sialic acid precursor treatment

  1. Get@NRC: Polysialic acid bioengineering of neuronal cells by N-acyl sialic acid precursor treatment (Opens in a new window)
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Journal titleGlycobiology
Pages249260; # of pages: 12
SubjectACID; Acids; Affect; analysis; Animals; Antibodies; Antibodies,Monoclonal; antibody; Biomedical Engineering; biosynthesis; Canada; cell; Cell Line,Tumor; Cell Membrane; CELLS; chemistry; Down-Regulation; drug effects; EXPRESSION; Flow Cytometry; GROUP-B; Hexosamines; Human; Humans; immunology; metabolism; Methods; Mice; MOLECULE; MONOCLONAL-ANTIBODIES; MONOCLONAL-ANTIBODY; N-Acetylneuraminic Acid; Neurons; PATHWAY; pharmacology; POLYSACCHARIDE; Polysaccharides; Polysaccharides,Bacterial; SIALIC; Sialic Acids; SIALIC-ACID; surface; SYSTEM; ultrastructure
AbstractThe inherent promiscuity of the polysialic acid (PSA) biosynthetic pathway has been exploited by the use of exogenous unnatural sialic acid precursor molecules to introduce unnatural modifications into cellular PSA, and has found applications in nervous system development and tumor vaccine studies. The sialic acid precursor molecules N-propionyl- and N-butanoyl-mannosamine (ManPr, ManBu) have been variably reported to affect PSA biosynthesis ranging from complete inhibition to de novo production of modified PSA, thus illustrating the need for further investigation into their effects. In this study, we have used a monoclonal antibody (mAb) 13D9, specific to both N-propionyl-PSA and N-butanoyl-PSA (NPrPSA and NBuPSA), together with flow cytometry, to study precursor-treated tumor cells and NT2 neurons at different stages of their maturation. We report that both ManPr and ManBu sialic acid precursors are metabolized and the resultant unnatural sialic acids are incorporated into de novo surface sialylglycoconjugates in murine and human tumor cells and, for the first time, in human NT2 neurons. Furthermore, neither precursor treatment deleteriously affected endogenous PSA expression; however, with NT2 cells, PSA levels were naturally downregulated as a function of their maturation into polarized neurons independent of sialic acid precursor treatment
Publication date
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberPON2007
NPARC number9372464
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Record identifier599de1af-e3b7-4bae-a79c-01bb1cc1ae8c
Record created2009-07-10
Record modified2016-05-09
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