The role of the ENaC-regulatory complex in aldosterone-mediated sodium transport

Soundararajan, Rama; Pearce, David; Ziera, Tim

doi:10.1016/j.mce.2011.11.003

Cited by 57 publications

(38 citation statements)

References 72 publications

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“…Dysregulation of ENaC may affect a variety of functions including deranged regulation of renal salt excretion [45], blood pressure [29], cell volume [46], fluid transport in the lung [47,48], endothelial function [49] and embryo implantation [50]. To which extent SPAK or WNK sensitive activation of SPAK participates in the regulation of those functions remains to be established.…”

Section: Discussionmentioning

confidence: 99%

SPAK Sensitive Regulation of the Epithelial Na<sup>+</sup> Channel ENaC

Ahmed

Salker²,

Elvira³

et al. 2015

Kidney Blood Press Res

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Background/Aims: The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na⁺,K⁺,2Cl^- cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na⁺ channel (ENaC). Methods: ENaC was expressed in Xenopus oocytes with or without additional expression of wild type SPAK, constitutively active ^T233ESPAK, WNK insensitive ^T233ASPAK or catalytically inactive ^D212ASPAK, and ENaC activity estimated from amiloride (50 µM) sensitive current (I_amil) in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine I_amil in colonic tissue from wild type mice (spak^wt/wt) and from gene targeted mice carrying WNK insensitive SPAK (spak^tg/tg). Results: I_amil was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes I_amil was significantly increased following coexpression of wild-type SPAK and ^T233ESPAK, but not following coexpression of ^T233ASPAK or ^D212ASPAK. Colonic I_amil was significantly higher in spak^wt/wt than in spak^tg/tg mice. Conclusion: SPAK has the potential to up-regulate ENaC.

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Section: Discussionmentioning

confidence: 99%

SPAK Sensitive Regulation of the Epithelial Na<sup>+</sup> Channel ENaC

Ahmed

Salker²,

Elvira³

et al. 2015

Kidney Blood Press Res

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“…8,11,23 Classically, sodium transport into kidney collecting ducts is mediated by aldosterone/MR induction of ENaCα. 53 ENaCα is also expressed in Müller cells 37,38,54 and may influence cell function, 17,54 although how this occurs is not fully understood. Recent studies identified that MR is expressed in Müller cells, 23,37,38 and furthermore, aldosterone and the MR stimulated the expression of ENaCα in Müller cells.…”

Section: Discussionmentioning

confidence: 99%

Retinal Vasculopathy Is Reduced by Dietary Salt Restriction

Deliyanti

Armani

Casely

et al. 2014

ATVB

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Objective— Neovascularization and vaso-obliteration are vision-threatening events that develop by interactions between retinal vascular and glial cells. A high-salt diet is causal in cardiovascular and renal disease, which is linked to modulation of the renin–angiotensin–aldosterone system. However, it is not known whether dietary salt influences retinal vasculopathy and if the renin–angiotensin–aldosterone system is involved. We examined whether a low-salt (LS) diet influenced vascular and glial cell injury and the renin–angiotensin–aldosterone system in ischemic retinopathy. Approach and Results— Pregnant Sprague Dawley rats were fed LS (0.03% NaCl) or normal salt (0.3% NaCl) diets, and ischemic retinopathy was induced in the offspring. An LS diet reduced retinal neovascularization and vaso-obliteration, the mRNA and protein levels of the angiogenic factors, vascular endothelial growth factor, and erythropoietin. Microglia, which influence vascular remodeling in ischemic retinopathy, were reduced by LS as was tumor necrosis factor-α. Macroglial Müller cells maintain the integrity of the blood–retinal barrier, and in ischemic retinopathy, LS reduced their gliosis and also vascular leakage. In retina, LS reduced mineralocorticoid receptor, angiotensin type 1 receptor, and renin mRNA levels, whereas, as expected, plasma levels of aldosterone and renin were increased. The aldosterone/mineralocorticoid receptor–sensitive epithelial sodium channel alpha (ENaCα), which is expressed in Müller cells, was increased in ischemic retinopathy and reduced by LS. In cultured Müller cells, high salt increased ENaCα, which was prevented by mineralocorticoid receptor and angiotensin type 1 receptor blockade. Conversely, LS reduced ENaCα, angiotensin type 1 receptor, and mineralocorticoid receptor expression. Conclusions— An LS diet reduced retinal vasculopathy, by modulating glial cell function and the retinal renin–angiotensin–aldosterone system.

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“…During the past 15 years, considerable progress has been made in the characterization of these cellular events, and numerous aldosteroneinduced proteins have been identified, including serum-and glucocorticoid-dependent kinase 1 (SGK1) (10,33), glucocorticoid-induced leucine zipper protein (GILZ) (40), the adaptor protein 14-3-3␤ (26), scaffold protein connector enhancer of kinase suppressor of RAS isoform 3 (CNK3) (49), or the deubiquitylating enzyme USP2-45 (14). Importantly, evidence has been provided that these proteins form a complex which may regulate ENaC function via posttranslational modifications including ubiquitylation (i.e., the posttranslational modification of target proteins with ubiquitin) (11,26,48). Ubiquitylation is now recognized as an essential mechanism for regulating cellular and physiological processes (12,43,54).…”

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confidence: 99%