Oxidized glutathione (GSSG) inhibits epithelial sodium channel activity in primary alveolar epithelial cells

Downs, Charles A.; Kreiner, Lisa; Zhao, Xing‐Ming; Trac, Phi T.; Johnson, Nicholle M.; Hansen, Jason M.; Brown, Lou Ann S.; Helms, My N.

doi:10.1152/ajplung.00213.2014

Cited by 21 publications

(17 citation statements)

References 51 publications

(63 reference statements)

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“…Reactive oxidants have also been shown to alter ENaC activity by either posttranslational modifications (such as oxidation, nitration, nitrosylation, and glutathionylation of critical residues) or through activation of signal transduction pathways (96). Furthermore, oxidized glutathione has been shown to inhibit ENaC activity in primary alveolar epithelial cells (18,33). Lazrak et al (54) measured the induction of reactive oxygen species (ROS) by M2 overexpression.…”

Section: Inhibition Of Enac and Cftr By Influenza Virus M2 Proteinmentioning

confidence: 99%

Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

Londino

Lazrak

Collawn

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl) and bicarbonate ([Formula: see text]) secretion and sodium (Na) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial periciliary fluid (PCL) and alveolar lining fluid (ALF) layers. The PCL is required for proper mucociliary clearance of pathogens and debris, and the ALF is necessary for surfactant homeostasis and optimum gas exchange. Dysregulation of ion transport may lead to mucus accumulation, bacterial infections, inflammation, pulmonary edema, and compromised respiratory function. Influenza (or flu) in mammals is caused by influenza A and B viruses. Symptoms include dry cough, sore throat, and is often followed by secondary bacterial infections, accumulation of fluid in the alveolar spaces and acute lung injury. The underlying mechanisms of flu symptoms are not fully understood. This review summarizes our present knowledge of how influenza virus infections alter airway and alveolar epithelial cell CFTR and ENaC function in vivo and in vitro and the role of these changes in influenza pathogenesis.

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Section: Inhibition Of Enac and Cftr By Influenza Virus M2 Proteinmentioning

confidence: 99%

Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

Londino

Lazrak

Collawn

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…We have previously shown that ENaC activity is dependent on levels of ROS, particularly superoxide (25)(26)(27)(28). We felt that our observed results were due to excess mitochondrial ROS production, but TEMPOL reduces ROS throughout the cell.…”

Section: The Role Of Rosmentioning

confidence: 78%

Knockout of mitochondrial voltage-dependent anion channel type 3 increases reactive oxygen species (ROS) levels and alters renal sodium transport

Zou

Linck

Zhai

et al. 2018

Journal of Biological Chemistry

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It has been suggested that voltage-dependent anion channels (VDACs) control the release of superoxide from mitochondria. We have previously shown that reactive oxygen species (ROS) such as superoxide (O) and hydrogen peroxide (HO) stimulate epithelial sodium channels (ENaCs) in sodium-transporting epithelial tissue, including cortical collecting duct (CCD) principal cells. Therefore, we hypothesized that VDACs could regulate ENaC by modulating cytosolic ROS levels. Herein, we find that VDAC3-knockout(KO) mice can maintain normal salt and water balance on low-salt and high-salt diets. However, on a high-salt diet for 2 weeks, VDAC3-KO mice had significantly higher systolic blood pressure than wildtype mice. Consistent with this observation, after a high-salt diet for 2 weeks, ENaC activity in VDAC3-KO mice was significantly higher than wildtype mice. EM analysis disclosed a significant morphological change of mitochondria in the CCD cells of VDAC3-KO mice compared with wildtype mice, which may have been caused by mitochondrial superoxide overload. Of note, compared with wildtype animals, ROS levels in VDAC3-KO animals fed a normal or high-salt diet were consistently and significantly increased in renal tubules. Both the ROS scavenger 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL) and the mitochondrial ROS scavenger (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mito-TEMPO) could reverse the effect of high-salt on ENaC activity and systolic blood pressure in the VDAC3-KO mice. Mito-TEMPO partially correct the morphological changes in VDAC3-KO mice. Our results suggest that knocking out mitochondrial VDAC3 increases ROS, alters renal sodium transport, and leads to hypertension.

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“…In resting cells, no more that 50 μmol L −1 of GSSG could be detected and thus experimental settings described in Ref. clearly represent conditions of severe oxidative stress. On the other hand, application of an antioxidant N‐acetylcystein (NAC) inhibited amiloride‐sensitive current in nasal epithelial cells .…”

Section: Discussionmentioning

confidence: 98%

“…It should be also noted that millimolar concentrations of H 2 O 2 used in those studies are clearly out of the physiological limits of DUOX‐mediated H 2 O 2 production. In this respect, it is interesting to mention that application of 400 μmol L −1 oxidized glutathione (GSSG) directly to primary rat epithelial Type II cells induced decrease in ENaC open probability . In resting cells, no more that 50 μmol L −1 of GSSG could be detected and thus experimental settings described in Ref.…”

Section: Discussionmentioning

confidence: 99%

DUOX1‐mediated hydrogen peroxide release regulates sodium transport in H441 bronchiolar epithelial cells

et al. 2018

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Oxidized glutathione (GSSG) inhibits epithelial sodium channel activity in primary alveolar epithelial cells

Abstract: Downs CA, Kreiner L, Zhao XM, Trac P, Johnson NM, Hansen JM, Brown LA, Helms MN. Oxidized glutathione (GSSG) inhibits epithelial sodium channel activity in primary alveolar epithelial cells.

Cited by 21 publications

References 51 publications

Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae

Knockout of mitochondrial voltage-dependent anion channel type 3 increases reactive oxygen species (ROS) levels and alters renal sodium transport

DUOX1‐mediated hydrogen peroxide release regulates sodium transport in H441 bronchiolar epithelial cells

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