Regulation of beta-galactoside alpha 2,6-sialyltransferase gene expression by dexamethasone.
The hepatic acute phase response is accompanied by increased levels of Gal beta 1-4GlcNAc alpha 2,6-sialyltransferase activity in liver and in circulation. Previous studies suggested that cytokines and glucocorticoids mediate the induction of this sialyltransferase activity. In this study the regulation of sialyltransferase expression by dexamethasone in H35 rat hepatoma cells is assessed by Northern hybridization and enzyme activity assays. Exposure of H35 cells to 1 microM dexamethasone for 24 h causes a 3-4-fold enrichment of sialyltransferase mRNA and a corresponding increase in enzymatic activity. The induction of sialyltransferase mRNA begins within 3 h of dexamethasone treatment and reaches a plateau within 24 h. Sialyltransferase mRNA induction is dose dependent; the minimum concentration of dexamethasone necessary for induction is 10(-8) M, and induction was maximal at 10(-6) M. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Puromycin and cycloheximide are ineffective in blocking induction, suggesting that de novo protein synthesis is not required for induction. Finally, dexamethasone alone is sufficient for maximum induction of sialyltransferase mRNA. In contrast, maximal induction of alpha 1-acid glycoprotein, a well studied hepatic acute phase reactant, requires both dexamethasone and cytokines, implying that different pathways exist for the induction of participants in the acute phase response.
Wang
X C
XC
Department of Molecular and Cellular Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.
O'Hanlon
T P
TP
Lau
J T
JT
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012799:Sialyltransferases / Q000235:genetics*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D012333:RNA, Messenger; D003907:Dexamethasone; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase