Biologic contribution of P1 promoter–mediated expression of ST6Gal I sialyltransferase

The synthesis of the common and well-documented Siaα2,6 to Galβ1,4GlcNAc structure (Sia6LacNAc) is principally mediated by the sialyltransferase ST6Gal I, which is particularly highly expressed in liver, lactating mammary gland, intestinal epithelia of newborn animals, and B cells. Multiple independ...

Full description

Saved in:
Bibliographic Details
Published in:Glycobiology (Oxford) 2003-08, Vol.13 (8), p.591-600
Main Authors: Appenheimer, Michelle M., Huang, Ruea-Yea, Chandrasekaran, E.V., Dalziel, Martin, Hu, Yi Ping, Soloway, Paul D., Wuensch, Sherry A., Matta, Khushi L., Lau, Joseph T.Y.
Format: Article
Language:English
Subjects:
(4-hydroxy-3-nitrophenyl)acetyl
acute phase response
Acute-Phase Reaction - enzymology
Acute-Phase Reaction - immunology
Acute-Phase Reaction - microbiology
Animals
APR
benzyl
bovine serum albumin
BSA
CFU
colony-forming units
ELISA
embryonic stem
enzyme-linked immunosorbent assay
FACS
Female
fluorescence-assisted cell sorting
gene expression
Gene Expression Regulation, Enzymologic
immune response
inflammation
Liver - microbiology
Male
Mice
Mice, Inbred C57BL
Neutrophils - immunology
Organ Specificity
PBS
phosphate buffered saline
Promoter Regions, Genetic - genetics
Recombination, Genetic - genetics
Salmonella Infections - enzymology
Salmonella Infections - immunology
Salmonella Infections - microbiology
Salmonella typhimurium
Salmonella typhimurium - immunology
Sambucus nigra agglutinin
SDS–PAGE
Sequence Deletion - genetics
sialyltransferase
Sialyltransferases - genetics
Sialyltransferases - immunology
Sialyltransferases - metabolism
SNA
sodium dodecyl sulfate–polyacrylamide gel electrophoresis
Spleen - microbiology
ST6Gal
wild-type
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The synthesis of the common and well-documented Siaα2,6 to Galβ1,4GlcNAc structure (Sia6LacNAc) is principally mediated by the sialyltransferase ST6Gal I, which is particularly highly expressed in liver, lactating mammary gland, intestinal epithelia of newborn animals, and B cells. Multiple independent promoters govern the expression of Siat1, the ST6Gal I gene. In liver, elevation of hepatic and serum ST6Gal is part of the acute phase reaction, the hepatic response to systemic trauma, and is governed by the inducible, liver-specific promoter-regulatory region, P1. A constitutive and nontissue-specific promoter, P3, mediates low-level, basal hepatic Siat1 transcription. We generated a mouse specifically unable to use the transcriptional initiation site uniquely used in P1-mediated ST6Gal I expression. These animals, Siat1ΔP1, are viable and display reduced ST6Gal I mRNA in liver with concomitantly reduced sialyltransferase activities in liver and in serum. Siat1ΔP1 animals are unable to elevate hepatic Siat1 mRNA as part of the inflammatory response induced by turpentine. Surprisingly, serum glycoprotein components exhibit normal extent of sialylation, with no noticeable difference in binding to SNA, the α2,6-sialyl-specific lectin. Siat1ΔP1 animals also exhibit an outwardly normal B cell response. On intraperitoneal challenge with the pathogen Salmonella typhimurium, a significantly greater accumulation of neutrophils within the peritoneal space was observed in Siat1ΔP1 animals compared to wild-type mice. Siat1ΔP1 mice also exhibit a greater bacterial burden in liver and spleen, accompanied by more pronounced spleno-/hepatomegaly and greater leukocyte infiltration into affected organs than their wild-type counterparts.
ISSN:0959-6658
1460-2423
1460-2423
DOI:10.1093/glycob/cwg066