Modulation of α-ENaC and α1-Na+-K+-ATPase by cAMP and dexamethasone in alveolar epithelial cells

Dagenais, André; Denis, Christine; Vives, Marie-France; Girouard, Sonia; Massé, Chantal; Nguyen, Thao; Yamagata, Toshiyuki; Grygorczyk, Czeslawa; Kothary, Rashmi; Berthiaume, Yves

doi:10.1152/ajplung.2001.281.1.l217

Cited by 94 publications

(119 citation statements)

References 62 publications

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“…Individual reports have proposed a role for cAMP in gene expression regulation of SCNN1A, ATP1A1/-B1, and NR3C2, [15][16][17]21 which are targets of endothelial aldosterone signaling. These observations, together with our results, suggested that sAC is involved in the regulation of all 4 genes and could affect endothelial stiffness.…”

Section: Expression Of Genes Regulating Endothelial Stiffness Dependsmentioning

confidence: 99%

“…11,13 Gene expression of ENaC-α (SCNN1A), Na + / K + -ATPase-α/-β (ATP1A1, ATP1B1), and the mineralocorticoid receptor (MR; NR3C2) has been suggested to depend on the second messenger cAMP. [14][15][16][17] The human adenylyl cyclase 10 (ADCY10), also termed soluble adenylyl cyclase (sAC), generates cAMP in the cellular nucleus 18,19 with subsequent protein kinase A (PKA) activation and cAMP response element-binding protein (CREB) phosphorylation. In the kidney, sAC has been reported to be involved in blood pressure homeostasis, whereas specific inhibition of sAC by its inhibitor KH7 resulted in abrogation of basic and agonist-stimulated Na + reabsorption.…”

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confidence: 99%

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Soluble Adenylyl Cyclase in Vascular Endothelium

et al. 2014

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Section: Expression Of Genes Regulating Endothelial Stiffness Dependsmentioning

confidence: 99%

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confidence: 99%

Soluble Adenylyl Cyclase in Vascular Endothelium

et al. 2014

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“…Na + transport can also be regulated by increased gene expression ( Figure 2). The two major hormones that modulate ENaC expression in the lung are catecholamines (Berthiaume, Y. et al 1999) and glucocorticoids (Dagenais, A. et al 2001). Like ENaC, modulation of Na + -K + -ATPase activity is complex and also involves the modulation of the trafficking of the protein to the membrane (Sznajder, J. I. et al 2002).…”

Section: Cellular Mechanisms Involved In Edema Clearancementioning

confidence: 99%

Alveolar edema fluid clearance and acute lung injury

Berthiaume

Matthay

2007

Respiratory Physiology & Neurobiology

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Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na + and Cl − transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na + and Cl − transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of β-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury.

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“…Alveolar epithelial cells were isolated from male Sprague-Dawley rats as described previously and according to a procedure approved by our institutional animal care committee (17). Perfused lungs were digested with elastase, and the cells were purified by a differential adherence technique on bacteriological plastic plates coated with rat IgG (17).…”

Section: Alveolar Epithelial Cell Isolation and Experimental Conditionsmentioning

confidence: 99%

“…Dexamethasone (Dex) is a synthetic steroid that has been shown to upregulate ENaC expression via a very conserved glucocorticoid regulatory element (GRE) in its promoter (15,17,63,74). Dex is also a well-known anti-inflammatory agent that has been used or proposed as a therapeutic approach to inflammatory disease, including lung injury (29).…”

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confidence: 99%

Dexamethasone inhibits the action of TNF on ENaC expression and activity

Dagenais

Fréchette²,

Clermont³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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We have reported that TNF, a proinflammatory cytokine present in several lung pathologies, decreases the expression and activity of the epithelial Na+channel (ENaC) by ∼70% in alveolar epithelial cells. Because dexamethasone has been shown to upregulate ENaC mRNA expression and is well known to downregulate proinflammatory genes, we tested if it could alleviate the effect of TNF on ENaC expression and activity. In cotreatment with TNF, we found that dexamethasone reversed the inhibitory effect of TNF and upregulated α, β, and γENaC mRNA expression. When the cells were pretreated for 24 h with TNF before cotreatment, dexamethasone was still able to increase αENaC mRNA expression to 1.8-fold above control values. However, in these conditions, β and γENaC mRNA expression was reduced to 47% and 14%, respectively. The potential role of TNF and dexamethasone on αENaC promoter activity was tested in A549 alveolar epithelial cells. TNF decreased luciferase (Luc) expression by ∼25% in these cells, indicating that the strong diminution of αENaC mRNA must be related to posttranscriptional events. Dexamethasone raised Luc expression by fivefold in the cells and augmented promoter activity by 2.77-fold in cotreatment with TNF. In addition to its effect on αENaC gene expression, dexamethasone was able to maintain amiloride-sensitive current as well as the liquid clearance abilities of TNF-treated cells within the normal range. All these results suggest that dexamethasone alleviates the downregulation of ENaC expression and activity in TNF-treated alveolar epithelial cells.

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Modulation of α-ENaC and α₁-Na⁺-K⁺-ATPase by cAMP and dexamethasone in alveolar epithelial cells

Cited by 94 publications

References 62 publications

Soluble Adenylyl Cyclase in Vascular Endothelium

Soluble Adenylyl Cyclase in Vascular Endothelium

Alveolar edema fluid clearance and acute lung injury

Dexamethasone inhibits the action of TNF on ENaC expression and activity

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