title: Developmental regulation of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (APOBEC-1) in human small intestine.
abstract: Apolipoprotein (apo) B mRNA editing is a site-specific cytidine deamination reaction responsible for the production of apoB-48 in mammalian small intestine. This process is mediated by an enzyme complex that includes the catalytic subunit, APOBEC-1. In the present study, it is shown that the developmental regulation of apoB mRNA editing in fetal human small intestine is closely mirrored by accumulation of APOBEC-1 mRNA. Similar results were obtained using Caco-2 cells, the data further suggesting that culture of these cells under conditions previously shown to promote differentiation produce an earlier and more marked induction of APOBEC-1 mRNA abundance. Complementary analysis of APOBEC-1 protein accumulation using immunocytochemical localization reveals its appearance to be temporally coordinated with the accumulation of APOBEC-1 mRNA and its distribution to be confined to villus-associated enterocytes. Previous studies demonstrated a close temporal association between the development of triglyceride synthesis and apoB mRNA editing in the rat liver and small intestine. Analysis of fatty acid CoA ligase, monoacylglycerol acyltransferase, and diacylglycerol acyltransferase activity in preparations of human liver and small intestine demonstrates activity of all three enzymes in the late first and early second trimester, suggesting that certain aspects of complex lipid biosynthesis in the human fetal small intestine and liver are regulated developmentally. The cues that modulate the post-transcriptional regulation of fetal human small intestinal apoB gene expression may thus include both temporal programming and events related to the emergence of lipid transport capability.
authors.affiliation: Department of Medicine, University of Chicago, IL 60637, USA.
authors.forename: F
authors.initials: F
authors.lastname: Giannoni
authors.forename: S C
authors.initials: SC
authors.lastname: Chou
authors.forename: S F
authors.initials: SF
authors.lastname: Skarosi
authors.forename: M S
authors.initials: MS
authors.lastname: Verp
authors.forename: F J
authors.initials: FJ
authors.lastname: Field
authors.forename: R A
authors.initials: RA
authors.lastname: Coleman
authors.forename: N O
authors.initials: NO
authors.lastname: Davidson
mesh_terms: D000071479:APOBEC-1 Deaminase; D000217:Acyltransferases / Q000378:metabolism; D000328:Adult; D001055:Apolipoproteins B; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D003066:Coenzyme A Ligases / Q000378:metabolism; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D051048:Diacylglycerol O-Acyltransferase; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000201:enzymology / Q000254:growth & development*; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D001055:Apolipoproteins B; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; C021802:2-acylglycerol O-acyltransferase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605091:Apobec1 protein, rat; D003564:Cytidine Deaminase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase