In our previous work we investigated the effects of O3, one of the most noxious pollutants to which respiratory tract is the most exposed organ, on Cl currents in human cultured lung epithelial cells (A549 line) and demonstrated that O3 exposure significantly affects Cl current, inducing a large outward rectifier component. Among the different types of chloride channels present on the cell membrane, Cl-C2 and ORCC (Outward Rectifier Chloride Channel) were the mainly involved, based on the experimental conditions. Functional experiments with specific channel blockers failed to uniquely identify the channel responsible for this stress induced behavior. In this study we show how silencing of the ANO6 gene (functional part of the ORCC channel) is able to completely eliminate the outward rectifier component of the current. Surprisingly, it was also observed that even under control conditions, a large part of the chloride current of the cell is sustained by the activity of this channel, usually considered inactive in the absence of oxidative stress or voltage stimulation. This work provides new explanations on the mechanisms of control of water-salt balance in lung epithelial cells at rest and subjected to oxidative stress.

Identification of the channel responsible for the ozone stress induced chloride current in human lung epithelial cells

Rita Canella
Primo
Conceptualization
;
Mascia Benedusi
Secondo
Investigation
;
Marta Martini
Investigation
;
Carlotta Cavicchio
Membro del Collaboration Group
;
Franco Cervellati
Membro del Collaboration Group
;
Giuseppe Valacchi
Ultimo
Supervision
2018

Abstract

In our previous work we investigated the effects of O3, one of the most noxious pollutants to which respiratory tract is the most exposed organ, on Cl currents in human cultured lung epithelial cells (A549 line) and demonstrated that O3 exposure significantly affects Cl current, inducing a large outward rectifier component. Among the different types of chloride channels present on the cell membrane, Cl-C2 and ORCC (Outward Rectifier Chloride Channel) were the mainly involved, based on the experimental conditions. Functional experiments with specific channel blockers failed to uniquely identify the channel responsible for this stress induced behavior. In this study we show how silencing of the ANO6 gene (functional part of the ORCC channel) is able to completely eliminate the outward rectifier component of the current. Surprisingly, it was also observed that even under control conditions, a large part of the chloride current of the cell is sustained by the activity of this channel, usually considered inactive in the absence of oxidative stress or voltage stimulation. This work provides new explanations on the mechanisms of control of water-salt balance in lung epithelial cells at rest and subjected to oxidative stress.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2394460
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