Mineralocorticoids Stimulate the Activity and Expression of Renal H+,K+-ATPases

Greenlee, Megan M.; Lynch, I. Jeanette; Gumz, Michelle L.; Cain, Brian D.; Wingo, Charles S.

doi:10.1681/asn.2010030311

Cited by 30 publications

(22 citation statements)

References 30 publications

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“…These observations led us to hypothesize that mice with reduced levels of Per1 would have increased urinary Na ϩ excretion. To determine if Per1 heterozygous mice excrete more Na ϩ , weight-matched male WT 129/sv and Per1 heterozygous mice were placed in metabolic cages, as previously described (15), and allowed to acclimate for 3 days. Per1 heterozygous mice were fed the same amount of food as the WT mice ate the previous day.…”

Section: Loss or Reduction Of Per1 Results In Increased Levels Of Crymentioning

confidence: 99%

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A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na⁺ retention

Richards

Cheng

All

et al. 2013

American Journal of Physiology-Renal Physiology

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The circadian clock plays an important role in the regulation of physiological processes, including renal function and blood pressure. We have previously shown that the circadian protein period (Per)1 regulates the expression of multiple Na+ transport genes in the collecting duct, including the α-subunit of the renal epithelial Na+ channel. Consistent with this finding, Per1 knockout mice exhibit dramatically lower blood pressure than wild-type mice. We have also recently demonstrated the potential opposing actions of cryptochrome (Cry)2 on Per1 target genes. Recent work by others has demonstrated that Cry1/2 regulates aldosterone production through increased expression of the adrenal gland-specific rate-limiting enzyme 3β-dehydrogenase isomerase (3β-HSD). Therefore, we tested the hypothesis that Per1 plays a role in the regulation of aldosterone levels and renal Na+ retention. Using RNA silencing and pharmacological blockade of Per1 nuclear entry in the NCI-H295R human adrenal cell line, we showed that Per1 regulates 3β-HSD expression in vitro. These results were confirmed in vivo: mice with reduced levels of Per1 had decreased levels of plasma aldosterone and decreased mRNA expression of 3β-HSD. We postulated that mice with reduced Per1 would have a renal Na+-retaining defect. Indeed, metabolic cage experiments demonstrated that Per1 heterozygotes excreted more urinary Na+ compared with wild-type mice. Taken together, these data support the hypothesis that Per1 regulates aldosterone levels and that Per1 plays an integral role in the regulation of Na+ retention.

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Section: Loss or Reduction Of Per1 Results In Increased Levels Of Crymentioning

confidence: 99%

“…Per1 heterozygous mice were fed what WT mice of a similar body weight ate the previous day. Fecal material was dried overnight at 200°C and digested in 0.75 N nitric acid overnight at 37°C, as previously described (15). Samples were then homogenized and filtered for analysis by flame photometry.…”

Section: Animalsmentioning

confidence: 99%

A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na⁺ retention

Richards

Cheng

All

et al. 2013

American Journal of Physiology-Renal Physiology

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“…gastric ciliated and mucocystic mataplasia (Judd et al, 2005; Spicer et al, 2000), and iron-deficiency (Krieg et al, 2011). Additionally, ATP4a loss of function affects ion homeostasis in the kidney (Greenlee et al, 2011; Lynch et al, 2008). Apart from these reports, we lack further knowledge on extragastric functions of ATP4a in the mouse.…”

Section: Discussionmentioning

confidence: 99%

ATP4a is required for development and function of the Xenopus mucociliary epidermis – a potential model to study proton pump inhibitor-associated pneumonia

Walentek

Beyer

Hagenlocher

et al. 2015

Developmental Biology

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Proton pump inhibitors (PPIs), which target gastric H+/K+ATPase (ATP4), are among the most commonly prescribed drugs. PPIs are used to treat ulcers and as a preventative measure against gastroesophageal reflux disease in hospitalized patients. PPI treatment correlates with an increased risk for airway infections, i.e. community- and hospital-acquired pneumonia. The cause for this correlation, however, remains elusive. The Xenopus embryonic epidermis is increasingly being used as a model to study airway-like mucociliary epithelia. Here we use this model to address how ATP4 inhibition may affect epithelial function in human airways. We demonstrate that atp4a knockdown interfered with the generation of cilia-driven extracellular fluid flow. ATP4a and canonical Wnt signaling were required in the epidermis for expression of foxj1, a transcriptional regulator of motile ciliogenesis. The ATP4/Wnt module activated foxj1 downstream of ciliated cell fate specification. In multiciliated cells (MCCs) of the epidermis, ATP4a was also necessary for normal myb expression, apical actin formation, basal body docking and alignment of basal bodies. Furthermore, ATP4-dependent Wnt/β-catenin signaling in the epidermis was a prerequisite for foxa1-mediated specification of small secretory cells (SSCs). SSCs release serotonin and other substances into the medium, and thereby regulate ciliary beating in MCCs and protect the epithelium against infection. Pharmacological inhibition of ATP4 in the mature mucociliary epithelium also caused a loss of MCCs and led to impaired mucociliary clearance. These data strongly suggest that PPI-associated pneumonia in human patients might, at least in part, be linked to dysfunction of mucociliary epithelia of the airways.

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“…Interestingly, the cell voltages of ICs are strikingly different from most cells, including principal cells: first, although there is little data, the cell-negative voltages as shown in Figure 4 are much less (less negative), and second, the cells are energized by the H 1 pump rather than by Na-K-ATPase as in most cells (54,57,58). H 1 secretion, including in the medullary collecting tubule, is also directly stimulated by mineralocorticoids, not just by secondary electrical effects (59,60). Distal tubule acidification may be strongly influenced by chloride concentration gradients between tubular lumen and peritubular blood; this may result both from voltage changes and by direct lumen to cell concentration gradients driving pendrin and other transporters.…”

Section: Regulation Of Acid-base Transporters In the Distal Nephronmentioning

confidence: 93%

Acid-Base Homeostasis

Hamm¹,

Nakhoul²,

Hering-Smith³

2015

Clinical Journal of the American Society of Nephrology

336

262

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Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO 3 2 and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO 3 2 is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

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Mineralocorticoids Stimulate the Activity and Expression of Renal H+,K+-ATPases

Abstract: In the renal collecting duct, mineralocorticoids drive Na ϩ reabsorption, K ϩ secretion, and H ϩ secretion through coordinated actions on apical and basolateral transporters.

Cited by 30 publications

References 30 publications

A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na⁺ retention

A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na⁺ retention

ATP4a is required for development and function of the Xenopus mucociliary epidermis – a potential model to study proton pump inhibitor-associated pneumonia

Acid-Base Homeostasis

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Mineralocorticoids Stimulate the Activity and Expression of Renal H+,K+-ATPases

Abstract: In the renal collecting duct, mineralocorticoids drive Na ϩ reabsorption, K ϩ secretion, and H ϩ secretion through coordinated actions on apical and basolateral transporters.

Cited by 30 publications

References 30 publications

A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention

A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention

ATP4a is required for development and function of the Xenopus mucociliary epidermis – a potential model to study proton pump inhibitor-associated pneumonia

Acid-Base Homeostasis

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Product

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A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na⁺ retention

A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na⁺ retention