Attenuation of NFkB Activation Augments Alveolar Transport Proteins Expression and Activity under Hypoxia

Epithelial sodium channels (ENaCs) controls vectorial Na across epithelia thus playing a central role in all aspects of fluid clearance in the body. The aim of this study was to investigate in vitro time dependant model of hypoxia induced reduction in vectorial Na and fluid transport across the alveolar epithelium. AEC exposed to 3% O2, for different time periods (1 h, 3h, 6h, 12h, 24h and 48 h) showed increased oxidative stress (↑ROS,↑MDA) and NF-κB up-regulation. Hypoxia induced a time-dependent decrease in Na/KATPase activity and α1 Na /K-ATPase protein expression reaching to negligible levels after 6h of exposure. Intriguingly, hypoxia also decreased copy number of ENaC α-subunit in AEC beyond detectable levels after 12h. Curcumin reinstate survival signalling by blunting NFkB signalling and reinforced the levels of alveolar antioxidants along with significant (p<0.001) increase in ENaC and Na/K-ATPase expression in lungs of rats under hypoxia. Therefore, we propose that, curcumin prophylaxis abate NFkB aberrant signalling induced down regulation of Na/K-ATPase and ENaC under hypoxia.