Aminophylline promotes mitochondrial biogenesis in human pulmonary bronchial epithelial cells.
Biochem Biophys Res Commun
; 515(1): 31-36, 2019 07 12.
Article
en En
| MEDLINE
| ID: mdl-31122698
ABSTRACT
Recently, mitochondrial dysfunction has been linked to the development of common airway disorders, such as chronic obstructive pulmonary disease (COPD) and asthma. Phosphodiesterase inhibitors are therapeutic agents for various diseases. Aminophylline is a nonselective phosphodiesterase inhibitor used to treat common lung diseases. In this study, we show that aminophylline promotes mitochondrial biogenesis in cultured human pulmonary bronchial epithelial cells (HPBECs). Aminophylline treatment induces the expression of transcriptional coactivator PGC-1α and transcriptional factors NRF1 and TFAM. The effect of aminophylline on mitochondrial biogenesis can be revealed by its promotion of the ratio of mitochondrial DNA to nuclear DNA (mtDNA/nDNA), mitochondrial protein cytochrome B and mitochondrial mass. At the cellular level, aminophylline increases the mitochondrial respiration rate and ATP production but reduces oxygen content. Consistently, we show that aminophylline activates the CREB-PGC-1α signaling pathway to promote mitochondrial biogenesis. The inhibition of CREB activation by its specific inhibitor H89 obscures the induction of PGC-1α, NRF1, and TFAM by aminophylline, and also abolishes the action of aminophylline on the mtDNA/nDNA ratio and respiration rate, suggesting that the activation of CREB is required for the action of aminophylline. Collectively, our study supports that aminophylline is a potent metabolic inducer of mitochondrial biogenesis in epithelial cells. Aminophylline could have a therapeutic effect on epithelial mitochondrial function in lung diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biogénesis de Organelos
/
Bronquios
/
Células Epiteliales
/
Aminofilina
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
China