Regulation of ENaC by 1,2‐propanediol, di‐2‐ethylhexyl phthalate and texanol

Abstract

The volatile organic compounds are potential causes of impaired respiratory system, such as shortness of breath, asthma, wheeze, etc. However, the molecular mechanisms of these symptoms caused by compounds in indoor air remain to be elucidated. In this study, we investigated the effects of 1,2‐propanediol, di‐2‐ethylhexyl phthalate (DEHP) and texanol on the epithelial Na+ channel (ENaC) activity in confluent H441 monolayers, a human bronchoalveolar epithelial cell line and in Xenopus oocytes heterologously expressing human αβγ ENaC. The Ussing chamber studies showed that propanediol (1mM) acutely increased amiloride‐sensitive (AS) short‐circuit current (Isc) levels by 13.7% when it was applied to the apical compartment. However, DEHP (1mM) and texanol (1mM) resulted in a slightly drop of AS Isc levels from 9.2 to 8.7 μA/cm2 and 10.7 to 9.0 μA/cm2, respectively (N=1). Chronically, these three compounds, when applied to the culture medium, increased the equivalent Isc levels in a time‐dependent manner in H441 monolayers. On day 3, Isc levels were increased by propanediol, DEHP, and texanol by 100.3%, 106.7% and 168.0%, respectively. These chronic effects were further corroborated with similar AS Isc in H441 cells using Ussing chamber setup. Taken together, our results suggest that propanediol, DEHP, and texanol lead to elevated ENaC activity in airway, which tightly correlates with airway surface fluid layer. Dehydrated airway may contribute to asthmatic dysfunction followed exposure to these noxious indoor air pollutants. Supported by HL087017 and HL095435.