References
Query Results -- Details
MGI Accession ID: MGI:3057047
J Number: J:93425
Other Accession IDs:
Title: Apobec-1 protects intestine from radiation injury through posttranscriptional regulation of cyclooxygenase-2 expression.
Authors: Anant S; Murmu N; Houchen CW; Mukhopadhyay D; Riehl TE; Young SG; Morrison AR; Stenson WF; Davidson NO
Journal: Gastroenterology
Volume: 127
Issue: 4
Date: 2004 Nov
Year: 2004
Pages: 1139-49
Review Status: Peer Reviewed
Abstract:
BACKGROUND & AIMS: This study aimed to determine the role of the RNA binding protein apobec-1 in radioprotection of the intestine. METHODS: Apobec-1-deleted mice (APOBEC-1(-/-)) and wild-type controls were treated with 12 Gy of whole-body gamma-irradiation in a cesium irradiator. The number of surviving intestinal crypts was assessed 3.5 days after irradiation by using a clonogenic assay. Cyclooxygenase-2 messenger RNA and protein expression were determined by real-time polymerase chain reaction and Western blot, respectively. RNA stability was studied by examining the turnover of a chimeric transcript containing the cyclooxygenase-2 3' untranslated region cloned downstream of luciferase complementary DNA. Apobec-1 binding to the cyclooxygenase-2 3' untranslated region was studied by electrophoretic mobility shift and UV crosslinking assays. RESULTS: After gamma-irradiation, the survival of intestinal stem cells decreased significantly in APOBEC-1(-/-) mice. In wild-type mice treated with lipopolysaccharide before gamma-irradiation, intestinal stem cells were protected by marked increases in prostaglandin E 2 mediated by cyclooxygenase-2. No such effect was observed in the APOBEC-1(-/-) mice. The mechanism of this radioprotective effect involves the binding of apobec-1 to AU-rich sequences in the first 60 nucleotides of the 3' untranslated region of cyclooxygenase-2. Upon binding to the AU-rich sequences, apobec-1 stabilizes cyclooxygenase-2 messenger RNA. This stabilization process does not seem to be mediated by p38 mitogen-activated protein kinase pathways. CONCLUSIONS: Lipopolysaccharide increases intestinal stem cell survival through apobec-1-mediated regulation of cyclooxygenase-2 messenger RNA stability.
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