Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis

Roy, Jeremy; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G.; Brown, Dennis; Breton, Sylvie

doi:10.1152/ajpcell.00410.2012

Cited by 18 publications

(19 citation statements)

References 63 publications

(110 reference statements)

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“…Double-immunofluorescence labeling for the B1 subunit of the VATPase (ATP6V1B1), specific for CCs, and clathrin, a subapical marker of CCs and PCs, was performed on cryosections, as previously described [12,24,42]. Sections were hydrated in PBS for 15 min and incubated in PBS containing 1% SDS (v/v) for 4 min.…”

Section: Immunofluorescence Labelingmentioning

confidence: 99%

“…The epididymal epithelium consists of different cell types including principal, narrow, clear, and basal cells that work together to establish an optimal environment. Narrow cells in the initial segment and clear cells (CCs) in the caput, corpus, cauda (Cd), and vas deferens secrete protons via the proton-pumping vacuolar (V-ATPase) located in their apical membrane [3,5,[11][12][13]. The V-ATPase is a major contributor to luminal acidification in several organs, including the kidney, airway, and osteoclast, in addition to the epididymis [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Relative contribution of clear cells and principal cells to luminal pH in the mouse epididymis†

Park¹,

Battistone²,

Kim³

et al. 2017

Biology of Reproduction

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While spermatozoa undergo epididymal maturation, they remain quiescent thanks to the establishment of a low luminal pH. This study is aimed at determining how epithelial cells lining the epididymal lumen work together to maintain and regulate this acidic milieu. In particular, we examined the relative contribution of clear cells (CCs) and principal cells (PCs) to this process. Functional analysis in the mouse cauda epididymidis (Cd) perfused in vivo showed that the pH of a control solution remained constant at pH 6.6 after perfusion through the Cd lumen. In contrast, the pH of both an acidic (pH 5.8) and alkaline (pH 7.8) perfusate was progressively restored toward the control acidic pH. Pharmacological studies indicated the contribution of cystic fibrosis transmembrane regulator, previously shown to be present in the apical membrane of PCs, to the recovery from an acidic pH of 5.8. In addition, we found that CCs and PCs equally contribute to the recovery from an alkaline of 7.8, via the H + pumping vacuolar ATPase (V-ATPase) located in CCs, and the Na + /H + exchanger type 3 (NHE3) located in PCs. Immunofluorescence labeling showed apical membrane accumulation of the V-ATPase in CCs at pH 7.8, and its internalization at pH 5.8 compared to pH 6.6. Immunofluorescence showed expression of NHE3, but absence of NHE2, in PCs located in the Cd. RT-PCR and western blotting showed expression of NHE3 in all epididymal regions. Luminal 8-(4-chlorophenylthio)adenosine 3 ,5 -cyclic monophosphate (cpt-cAMP) partially inhibited luminal pH recovery from pH 7.8. However, cpt-cAMP induced an increase in V-ATPase apical membrane accumulation at this pH. Cell fractionation studies showed the apical accumulation of NHE3 from intracellular vesicles at pH 7.8 versus 6.6, and prevention of this effect by cpt-cAMP. These results indicate the participation of both CCs and PCs in the regulation of luminal pH in the epididymis. Our study also shows the dual role of PCs in HCO 3 − and H + secretion, and that this switch from base to acid secretion depends on the luminal environment. Characterization of the respective roles of CCs and PCs in the regulation of the optimal luminal condition for epididymal sperm maturation should provide new frameworks for the evaluation and treatment of male infertility. Summary SentenceThis study shows the equal contribution of clear and principal cells to proton secretion, and the dual role of principal cells in bicarbonate and proton secretion, depending on luminal cues.

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Section: Immunofluorescence Labelingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relative contribution of clear cells and principal cells to luminal pH in the mouse epididymis†

Park¹,

Battistone²,

Kim³

et al. 2017

Biology of Reproduction

Self Cite

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“…Upon stimulation of translation, PI3K associates with the membrane skeleton [76] and triggers phosphorylation of 4E-BP1 [72,77] with subsequent dissociation of the inhibitory binding molecules, redistribution of the translation initiation factors close to mRNA [73] and translation of mRNA [75]. Mineralocorticoids may thus influence platelet protein expression by nongenomic mechanisms [78,79,79,80,81,82,83,84,85,86,87,88,89], including PI3K [90,91]. …”

Section: Discussionmentioning

confidence: 99%

Sgk1 Sensitive Pendrin Expression in Murine Platelets

Pelzl

Fakhri²,

Umbach³

et al. 2013

Cell Physiol Biochem

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Background: The anion exchanger pendrin (SLC26A4) is required for proper development of the inner ear, and contributes to iodide organification in thyroid glands as well as anion transport in various epithelia, such as airways and renal tubules. SLC26A4 deficiency leads to Pendred syndrome, which is characterized by hearing loss with enlarged vestibular aqueducts and variable hypothyroidism and goiter. Pendrin expression in kidney, heart, lung and thyroid is up-regulated by the mineralocorticoid deoxycorticosterone (DOCA). Platelets express anion exchangers but virtually nothing is known about the molecular identity and regulation of those carriers. Other carriers such as the Na⁺/H⁺ exchanger are regulated by the mineralocorticoid-sensitive serum and glucocorticoid inducible kinase SGK1. Methods: The present study utilized i) quantitative reverse transcription polymerase chain reaction (RT-qPCR) to quantify the transcript levels of Slc26a4 as compared to Gapdh and ii) western blotting to assess Slc26a4 protein abundance in murine platelets from gene-targeted mice lacking Sgk1 (sgk1^-/-) and respective wild type animals (sgk1^+/+) treated without or with a subcutaneous injection of 2.5 mg DOCA for 3 h, or in sgk1^+/+ platelets with or without in vitro treatment for 1 h with 10 µg/ml DOCA. Results: Slc26a4 was expressed in platelets, and in vitro DOCA treatment increased Slc26a4 mRNA levels in platelets isolated from sgk1^+/+ mice. Moreover, in vivo DOCA treatment significantly up-regulated Slc26a4 mRNA levels in platelets isolated from sgk1^+/+ but not sgk1^-/- mice. An increase in Sgk1 mRNA levels paralleled that of Slc26a4 mRNA levels in platelets of sgk1^+/+ mice. In addition, DOCA treatment further increased Slc26a4 protein abundance in platelets isolated from sgk1^+/+ mice. Conclusions: Pendrin is expressed in platelets and is presumably regulated by SGK1 and mineralocorticoids.

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“…Enhanced proton secretion is achieved rapidly within 15 min and most probably by influencing microtubule and PKC-dependent rapid trafficking of the pumps to the cell membrane (Gekle et al 1997, Winter et al 2004, Dos Santos et al 2009). These effects not only occur in kidney but also in other organs (Ehrenfeld et al 1985, Harvey 1992, Roy et al 2013. Again the effects of aldosterone on H + -ATPase seem to combine rapid nongenomic and genomic effects as it has been shown in proximal renal tubule (Leite-Dellova et al…”

Section: :1mentioning

confidence: 99%

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Nongenomic effects via the mineralocorticoid receptor

Ruhs

Nolze

Hübschmann

et al. 2017

Journal of Endocrinology

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The mineralocorticoid receptor (MR) belongs to the steroid hormone receptor family and classically functions as a ligand-dependent transcription factor. It is involved in water-electrolyte homeostasis and blood pressure regulation but independent from these effects also furthers inflammation, fibrosis, hypertrophy and remodeling in cardiovascular tissues. Next to genomic effects, aldosterone elicits very rapid actions within minutes that do not require transcription or translation and that occur not only in classical MR epithelial target organs like kidney and colon but also in nonepithelial tissues like heart, vasculature and adipose tissue. Most of these effects can be mediated by classical MR and its crosstalk with different signaling cascades. Near the plasma membrane, the MR seems to be associated with caveolin and striatin as well as with receptor tyrosine kinases like EGFR, PDGFR and IGF1R and G proteincoupled receptors like AT1 and GPER1, which then mediate nongenomic aldosterone effects. GPER1 has also been named a putative novel MR. There is a close interaction and functional synergism between the genomic and the nongenomic signaling so that nongenomic signaling can lead to long-term effects and support genomic actions. Therefore, understanding nongenomic aldosterone/MR effects is of potential relevance for modulating genomic aldosterone effects and may provide additional targets for intervention.

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Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis

Cited by 18 publications

References 63 publications

Relative contribution of clear cells and principal cells to luminal pH in the mouse epididymis†

Relative contribution of clear cells and principal cells to luminal pH in the mouse epididymis†

Sgk1 Sensitive Pendrin Expression in Murine Platelets

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Nongenomic effects via the mineralocorticoid receptor

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