Regulation of glycolipid synthesis in HL-60 cells by antisense oligodeoxynucleotides to glycosyltransferase sequences: effect on cellular differentiation.

Abstract	Treatment of the human promyelocytic leukemia cell line HL-60 with antisense oligodeoxynucleotides to UDP-N-acetylgalactosamine:beta-1,4-N-acetylgalactosaminyl-transferase (GM2-synthase; EC 2.4.1.92) and CMP-sialic acid:alpha-2,8-sialyltransferase (GD3-synthase; EC 2.4.99.8) sequences effectively down-regulated the synthesis of more complex gangliosides in the ganglioside synthetic pathways after GM3, resulting in a remarkable increase in endogenous GM3 with concomitant decreases in more complex gangliosides. The treated cells underwent monocytic differentiation as judged by morphological changes, adherent ability, and nitroblue tetrazolium staining. These data provide evidence that the increased endogenous ganglioside GM3 may play an important role in regulating cellular differentiation and that the antisense DNA technique proves to be a powerful tool in manipulating glycolipid synthesis in the cell.
Authors	G Zeng, T Ariga, X B Gu, R K Yu
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 92 Issue 19 Pg. 8670-4 (Sep 12 1995) ISSN: 0027-8424 [Print] United States
PMID	7567994 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Glycolipids Glycosphingolipids Oligonucleotides, Antisense Glycosyltransferases N-Acetylgalactosaminyltransferases polypeptide N-acetylgalactosaminyltransferase (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase Sialyltransferases alpha-N-acetylneuraminate alpha-2,8-sialyltransferase haematoside synthetase
Topics	Base Sequence Carbohydrate Sequence Cell Differentiation (drug effects) Cell Division Down-Regulation Gene Expression Regulation, Leukemic Glycolipids (biosynthesis) Glycosphingolipids (analysis) Glycosyltransferases (drug effects) Humans Leukemia, Promyelocytic, Acute (enzymology, genetics, metabolism) Molecular Sequence Data N-Acetylgalactosaminyltransferases (drug effects) Oligonucleotides, Antisense (pharmacology) Sialyltransferases (drug effects) Tumor Cells, Cultured

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