Regulation of ion transport by oxidants

Abstract

Ion channels perform a variety of cellular functions in lung epithelia. Oxidant- and antioxidant-mediated mechanisms (that is, redox regulation) of ion channels are areas of intense research. Significant progress has been made in our understanding of redox regulation of ion channels since the last Experimental Biology report in 2003. Advancements include: 1) identification of nonphagocytic NADPH oxidases as sources of regulated reactive species (RS) production in epithelia, 2) an understanding that excessive treatment with antioxidants can result in greater oxidative stress, and 3) characterization of novel RS signaling pathways that converge upon ion channel regulation. These advancements, as discussed at the 2013 Experimental Biology Meeting in Boston, MA, impact our understanding of oxidative stress in the lung, and, in particular, illustrate that the redox state has profound effects on ion channel and cellular function.

Receptor for Advanced Glycation End-Products Regulates Lung Fluid Balance via Protein Kinase C–gp91phox Signaling to Epithelial Sodium Channels

“…Recently, PKC isoforms have been shown to phosphorylate the p47 phox subunit of Nox leading to assembly and activation. We, and others have recently shown that the seven Nox isoforms (Nox1-5, dual oxidase 1, and dual oxidase 2) are expressed in the human lung, albeit the cellular distribution of each Nox isoform in the human lung remains unclear (27). Importantly, we have shown that Nox2-derived reactive oxygen species (ROS) are critical regulators of lung ENaC activity (28,29).…”

Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments

“…More precisely, CS-induced oxidative stress has been correlated with the disruption of selective ion channels within the lung epithelium (33,95). These ion channels are vital for certain cellular processes and when obstructed, may markedly enhance chronic lung inflammation.…”

“…Specifically, the hindrance of a chloride and bicarbonate channel associated with the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with difficulties in mucus transport, poor airway hydration, and disease susceptibility in COPD (95). Furthermore, ROS may interfere with the oxidative regulation of amiloride-and ROS-sensitive epithelial sodium channels (ENaC), responsible for the reabsorption of sodium and water (33). ENaC activity is regulated by the production of NOX, which is the rate-limiting factor in edema resolution in the lung; any ROS-induced inhibition of ion channel activity may drastically impede fluid clearance, heighten the inflammatory response, and disrupt the endothelial cell barrier (33).…”

“…Furthermore, ROS may interfere with the oxidative regulation of amiloride-and ROS-sensitive epithelial sodium channels (ENaC), responsible for the reabsorption of sodium and water (33). ENaC activity is regulated by the production of NOX, which is the rate-limiting factor in edema resolution in the lung; any ROS-induced inhibition of ion channel activity may drastically impede fluid clearance, heighten the inflammatory response, and disrupt the endothelial cell barrier (33).…”

A critical review of the American Journal of Physiology-Lung Cellular and Molecular Physiology: 2012–2015

“…Again I refer the readers to the Physiology in Medicine review by Dr. Chatterjee (7) as well as a comprehensive review on the role of NAPDH in the regulation of lung amiloride-sensitive epithelial sodium channels (13). On this topic, Sharma et al (49) showed that activation of ATII cell NADPH during ischemiareperfusion injury leads to the production of CXCL1, which contributes to the recruitment and activation of neutrophils and lung injury.…”