DUOX1-mediated hydrogen peroxide release regulates sodium transport in H441 bronchiolar epithelial cells.
Acta Physiol (Oxf)
; 225(1): e13166, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30052308
AIM: Dexamethasone has been shown to induce the formation of epithelial domes by bronchiolar H441 cells. It stimulates the expression of both amiloride inhibitable epithelial sodium channels (ENaC) and dual oxidase-1 (DUOX1). We therefore ask the question whether DUOX1 expression and production of submillimolar amounts of H2 O2 is instrumental for the sodium channel upregulation observed in H441 cells. METHODS: In vitro cell culture, nystatin-perforated whole-cell patch-clamp technique, immunocytochemistry and RT-PCR methods have been used. RESULTS: Cells forming epithelial domes induced by dexamethasone (0.1 µmol L-1 , 24 hours) and by 5-aza-2'-deoxytidine (1 µmol L-1 , 48 hours) expressed more DUOX1 protein compared with other cells in the monolayer. Dome formation could be inhibited by exogenous catalase in a concentration-dependent manner and by the NADPH oxidase inhibitor diphenyliodonium, which suggested the involvement of H2 O2 . While single application of 0.2 mmol L-1 H2 O2 induced transient dome formation, lower doses were ineffective and higher doses disrupted the cell monolayer. Hydrogen peroxide (0.1 mmol L-1 ) activated acutely amiloride-sensitive whole-cell currents from 3.91 ± 0.79 pA pF-1 to 4.76 ± 0.98 pA pF-1 in dome-forming cells and had no effect in cells outside of domes. ENaC but not DUOX1 transcription was potentiated by catalase in the presence of dexamethasone, which suggested negative feedback of H2 O2 on ENaC gene expression. CONCLUSION: Our observations suggest that tonic production of H2 O2 by DUOX1 participates in maintaining the level of vectorial sodium transport by lung epithelial cells. Moreover, the system appears to be well tuned as it would allow H2 O2 -dependent innate immunity without inducing airway/alveolar sodium and fluid hyperabsorption.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sodio
/
Células Epiteliales
/
Oxidasas Duales
/
Peróxido de Hidrógeno
Límite:
Humans
Idioma:
En
Revista:
Acta Physiol (Oxf)
Asunto de la revista:
FISIOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Bélgica
Pais de publicación:
Reino Unido