New ideas about aldosterone signaling in epithelia

Stockand, James D.

doi:10.1152/ajprenal.00320.2001

Cited by 149 publications

(124 citation statements)

References 204 publications

(210 reference statements)

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“…Nor can we explain how differences in the acute adrenocortical stress response influenced toad physiology to produce differences in water loss and survival responses. Based on existing knowledge, it is plausible to suggest that more responsive experimental adrenocortical stress phenotypes induced rapid activation of GC and mineralocorticoid receptors via crosstalk feedback mechanisms [43], increasing water loss and thus reducing survival. GC-receptor activation could result in lower upregulation of genes and proteins necessary for increases in Na þ absorption in the kidneys and urinary bladder, which are necessary to maintain osmotic balance [29,30].…”

Section: Discussionmentioning

confidence: 99%

Adrenocortical stress responses influence an invasive vertebrate's fitness in an extreme environment

et al. 2013

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Continued range expansion into physiologically challenging environments requires invasive species to maintain adaptive phenotypic performance. The adrenocortical stress response, governed in part by glucocorticoid hormones, influences physiological and behavioural responses of vertebrates to environmental stressors. However, any adaptive role of this response in invasive populations that are expanding into extreme environments is currently unclear. We experimentally manipulated the adrenocortical stress response of invasive cane toads (Rhinella marina) to investigate its effect on phenotypic performance and fitness at the species' range front in the Tanami Desert, Australia. Here, toads are vulnerable to overheating and dehydration during the annual hot -dry season and display elevated plasma corticosterone levels indicative of severe environmental stress. By comparing unmanipulated control toads with toads whose adrenocortical stress response was manipulated to increase acute physiological stress responsiveness, we found that control toads had significantly reduced daily evaporative water loss and higher survival relative to the experimental animals. The adrenocortical stress response hence appears essential in facilitating complex phenotypic performance and setting fitness trajectories of individuals from invasive species during range expansion.

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Section: Discussionmentioning

confidence: 99%

Adrenocortical stress responses influence an invasive vertebrate's fitness in an extreme environment

et al. 2013

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“…The effects of aldosterone include transcriptional, translational, and post-translational modifications of ENaC and involve a complex system of aldosterone-induced and/or aldosterone-repressed regulatory proteins (13). Despite impressive progress in this field of research the molecular mechanisms that mediate the stimulatory effect of aldosterone on ENaC activity remain incompletely understood (14). However, there is a growing body of evidence that the serum-and glucocorticoid-inducible kinase isoform 1 (SGK1) is an important contributing factor in the signal transduction cascade of aldosterone action on epithelial sodium transport (15).…”

mentioning

confidence: 99%

A Novel Pathway of Epithelial Sodium Channel Activation Involves a Serum- and Glucocorticoid-inducible Kinase Consensus Motif in the C Terminus of the Channel's α-Subunit

Diakov

Korbmacher

2004

Journal of Biological Chemistry

155

145

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Aldosterone-induced serum-and glucocorticoid-inducible kinase isoform 1 (SGK1) contributes to the regulation of the epithelial sodium channel (ENaC), the activity of which is critical for long term blood pressure control. Aldosterone-induced SGK1 is thought to enhance ENaC surface expression by phosphorylating Nedd4-2 and thereby preventing ENaC retrieval and degradation. In outside-out membrane patches of Xenopus laevis oocytes heterologously expressing ENaC, amiloride-sensitive ENaC currents were enhanced by phosphatase inhibitors and were dependent on cytosolic Mg 2؉ . This indicates that a kinase is involved in channel regulation. Indeed, recombinant constitutively active SGK1, included in the pipette solution, caused a sustained 2-to 3-fold increase of ENaC currents. Deletion of the C terminus of ␣ENaC largely reduced the stimulatory effect of SGK1, whereas stimulation by SGK1 did not require the presence of the C termini of the ␤-or ␥-subunits. Replacing the serine residue Ser 621 of the SGK1 consensus motif in the C terminus of the ␣-subunit by an alanine specifically abolished the stimulatory effect of SGK. Our findings indicate that SGK1 can stimulate ENaC activity independently of an inhibition of Nedd4-2-mediated channel retrieval. This defines a novel regulatory pathway likely to be relevant for aldosterone-induced stimulation of ENaC in vivo.The appropriate regulation of the epithelial sodium channel (ENaC) 1 in the kidney is critically important for the maintenance of body sodium balance and hence for long term regulation of arterial blood pressure (1). Indeed, two human genetic diseases provide direct evidence that molecular dysfunction of ENaC has severe effects on arterial blood pressure. Loss-offunction mutations of ENaC cause urinary sodium loss, hyperkalemia, and low blood pressure in patients with pseudohypoaldosteronism type 1 (2). In contrast, gain-of-function mutations of ENaC are found in patients with so-called Liddle's syndrome (pseudohyperaldosteronism) and result in increased renal sodium re-absorption, hypokalemia, and severe arterial hypertension (3).ENaC is composed of three subunits called ␣, ␤, and ␥ (4). The C termini of the ENaC subunits each contain a proline-rich PPXY (PY) motif, which is believed to be important for interaction with the ubiquitin-protein ligases Nedd4 and Nedd4-2, promoting the ubiquitination, endocytosis, and proteasomal degradation of the channel (5-8). The functional importance of the PY motif was recognized in Liddle's syndrome where mutations and/or deletions of the PY motif in ␤ or ␥ ENaC reduce the endocytic retrieval of ENaC from the membrane (9, 10). This results in an increase in the number of ENaC channels in the membrane, which in turn is thought to cause hyperabsorption of Na ϩ and hypertension in patients with Liddle's syndrome (11,12).The most important hormone to regulate ENaC activity is the mineralocorticoid aldosterone. The effects of aldosterone include transcriptional, translational, and post-translational modifications of ENaC and inv...

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“…The genomic late phase results from both primary and secondary effects on gene expression. One of the early ALDO-induced proteins is Sgk1, a serinethreonine kinase [234,235]. Presumably, Sgk1 binds and phosphorylates the ENaC regulatory protein (Nedd4-2) to reduce its binding to ENaC [236].…”

Section: Classic Genomic Actions Of Aldomentioning

confidence: 99%

“…In addition, during the early phase of genomic ALDO action, the expression of the small, monomeric Kirsten Ras GTP-binding protein-2A (Ki-RasA) is induced and required for the ALDO-mediated effects on Na + transport in renal epithelial cells. Ki-RasA appears to have dual contrasting effects on ENaC channels by i) keeping the channel open and ii) decreasing the number of channels in the plasma membrane [235,237,238]. The activity of the lipid kinase PI3K is increased by ALDO in the kidney [235,239], and the inhibition of PI3K reduces both the early and late genomic actions of ALDO [225].…”

Section: Classic Genomic Actions Of Aldomentioning

confidence: 99%

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ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

Mello-Aires¹,

Dellova²,

Castelo‐Branco³

et al. 2017

Nephrol Renal Dis

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This article reviews the main body of knowledge regarding NHE1 and NHE3 exchangers and their interaction with Angiotensin II, Angiotensin-(1-7), Aldosterone and Arginine Vasopressin, particularly their renal actions. This work addresses the biphasic effects of different hormonal doses on NHE1 or NHE3 in proximal tubule in Wistar, SHR (hypertensives) and their control WKY (normotensives) rats or MDCK cells (which share similarities with the collecting duct). The hormones were applied alone, with their inhibitors or plus agents that change the [Ca 2+ ]i. The data are compatible with hormonal stimulation of these exchangers by increases of [Ca 2+ ]i in lower range, and inhibition at high [Ca 2+ ]i. In MDCK cells and Wistar rats, low doses of ANG II, ALDO or AVP stimulated the exchangers, while high doses inhibited them. ANG-(1-7), in Wistar or WKY rats has inverse, dose-dependent effects. In SHR rats, the biphasic effects of ANG-(1-7) were similar to the effects of ANG II, ALDO or AVP in Wistar rats. The interactions between these effects may represent a mechanism that regulates extracellular volume. In hypertensives animals, a high plasma level of ANG-(1-7) inhibited NHE3 in the proximal tubule, which mitigated hypertension. Figure 6 shows a schematic model to describe these biphasic hormonal effects.

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New ideas about aldosterone signaling in epithelia

Cited by 149 publications

References 204 publications

Adrenocortical stress responses influence an invasive vertebrate's fitness in an extreme environment

Adrenocortical stress responses influence an invasive vertebrate's fitness in an extreme environment

A Novel Pathway of Epithelial Sodium Channel Activation Involves a Serum- and Glucocorticoid-inducible Kinase Consensus Motif in the C Terminus of the Channel's α-Subunit

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

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