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Titolo:
Modulation of alpha-ENaC and alpha(1)-Na+-K+-ATPase by cAMP and dexamethasone in alveolar epithelial cells
Autore:
Dagenais, A; Denis, C; Vives, MF; Girouard, S; Masse, C; Nguyen, T; Yamagata, T; Grygorczyk, C; Kothary, R; Berthiaume, Y;
Indirizzi:
Univ Montreal, Ctr Hosp Univ Montreal Hotel Dieu, Ctr Rech, Dept Med, Montreal, PQ H2W 1T8, Canada Univ Montreal Montreal PQ Canada H2W 1T8 ed, Montreal, PQ H2W 1T8, Canada Ottawa Gen Hosp, Res Inst, Ctr Mol Med, Ottawa, ON K1H 8L5, Canada Ottawa Gen Hosp Ottawa ON Canada K1H 8L5 Med, Ottawa, ON K1H 8L5, Canada
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
fascicolo: 1, volume: 281, anno: 2001,
pagine: L217 - L230
SICI:
1040-0605(200107)281:1<L217:MOAAAB>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NA+-K+-ATPASE; LUNG LIQUID CLEARANCE; BETA(1) SUBUNIT GENE; SODIUM-CHANNEL; RAT LUNG; 5'-FLANKING REGION; TRANSCRIPTIONAL REGULATION; DEVELOPMENTAL REGULATION; GLUCOCORTICOID HORMONE; BIOPHYSICAL PROPERTIES;
Keywords:
sodium channel; adenosine 3 ',5 '-cyclic monophosphate; steroid; sodium-potassium-adenosinetriphosphatase transepithelial current; epithelial sodium channel;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Dagenais, A Univ Montreal, Ctr Hosp Univ Montreal Hotel Dieu, Ctr Rech, Dept Med, 3840St Urbain, Montreal, PQ H2W 1T8, Canada Univ Montreal 3840 St Urbain Montreal PQ Canada H2W 1T8 Canada
Citazione:
A. Dagenais et al., "Modulation of alpha-ENaC and alpha(1)-Na+-K+-ATPase by cAMP and dexamethasone in alveolar epithelial cells", AM J P-LUNG, 281(1), 2001, pp. L217-L230

Abstract

cAMP and dexamethasone are known to modulate Na+ transport in epithelial cells. We investigated whether dibutyryl cAMP (DBcAMP) and dexamethasone modulate the mRNA expression of two key elements of the Nac transport system in isolated rat alveolar epithelial cells: alpha-, beta-, and gamma -subunits of the epithelial Na+ channel (ENaC) and the aland beta (1)-subunits of Na+-K+-ATPase. The cells were treated for up to 48 h with DBcAMP or dexamethasone to assess their long-term impact on the steady-state level of ENaC and Na+-K+-ATPase mRNA. DBcAMP induced a twofold transient increase of alpha -ENaC and alpha (1)-Na+-K+-ATPase mRNA that peaked after 8 h of treatment. It also upregulated beta- and gamma -ENaC mRNA but not beta (1)-Na+-K+-ATPase mRNA. Dexamethasone augmented alpha -ENaC mRNA expression 4.4-fold in cells treated for 24 h and also upregulated beta- and gamma -ENaC mRNA. Therewas a 1.6-fold increase at 8 h of beta (1)-Na+-K+-ATPase mRNA but no significant modulation of alpha (1)-Na+-K+-ATPase mRNA expression. Because DBcAMP and dexamethasone did not increase the stability of alpha -ENaC mRNA, we cloned 3.2 kb of the 5' sequences flanking the mouse alpha -ENaC gene to study the impact of DBcAMP and dexamethasone on alpha -ENaC promoter activity. The promoter was able to drive basal expression of the chloramphenicol acetyltransferase (CAT) reporter gene in A549 cells. Dexamethasone increased the activity of the promoter by a factor of 5.9. To complete the study, thephysiological effects of DBcAMP and dexamethasone were investigated by measuring transepithelial current in treated and control cells. DBcAMP and dexamethasone modulated transepithelial current with a time course reminiscentof the profile observed for alpha -ENaC mRNA expression. DBcAMP had a greater impact on transepithelial current (2.5-fold increase at 8 h) than dexamethasone (1.8-fold increase at 24 h). These results suggest that modulationof alpha -ENaC and Na+-K+-ATPase gene expression is one of the mechanisms that regulates Na+ transport in alveolar epithelial cells.

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Documento generato il 05/12/20 alle ore 14:04:41