13 209

Cited 0 times in

Multiple mechanisms for oxygen-induced regulation of the Clara cell secretory protein gene.

Ramsay, PL; Luo, Z; Major, A; Park, MS; Finegold, M; Welty, SE; Kwak, I; Darlington, G; Demayo, FJ
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 17(14):2142-2144, 2003
Journal Title
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
The Clara cell secretory protein (CCSP) imparts a protective effect to the lung during oxidant injury. However, exposure to supplemental oxygen, a common therapeutic modality for lung disease, represses the expression of CCSP in the adult mouse lung. We investigated the mechanisms of hyperoxia-induced repression of the mouse CCSP promoter. Deletion experiments in vivo and in vitro indicated that the hyperoxia-responsive elements are localized to the proximal -166 bp of the CCSP promoter. Electrophoretic mobility shift and supershift analyses demonstrated increased binding of c-Jun at the activator protein-1 site, increased binding of CCAAT/enhancer binding protein (C/EBP) beta at the C/EBP sites, and decreased binding at the Nkx2.1 sites. Western analyses revealed that hyperoxia exposure induced an increase in the expression of the C/EBPbeta isoform liver-inhibiting protein (LIP) and an increase in cytoplasmic Nkx2.1. Cotransfection of LIP or c-Jun expression plasmids decreased the transcriptional activity of the proximal -166-bp CCSP promoter. These observations suggest that hyperoxia-induced repression of the CCSP gene is mediated, at least in part, at the level of transcription and that multiple mechanisms mediate this repression. Moreover, these novel observations may provide insights for generation of therapeutic interventions for the amelioration of oxidant-induced lung injury.
MeSH terms
5' Flanking RegionAnimalsBinding SitesCCAAT-Enhancer-Binding Protein-beta/metabolismCell Line, TransformedCytoplasm/chemistryGene Silencing*Homeodomain Proteins/analysisMiceModels, GeneticOxygen/toxicityProteins/genetics*Proteins/metabolismProto-Oncogene Proteins c-jun/metabolismRegulatory Sequences, Nucleic AcidTranscription Factors/metabolismTranscription, GeneticUteroglobin*
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pediatrics & Adolescent Medicine
AJOU Authors
박, 문성
Full Text Link
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.