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Epithelial sodium channel abundance is decreased by an unfolded protein response induced by hyperosmolality.

Crambert G, Ernandez T, Lamouroux C, Roth I, Dizin E, Martin PY, Féraille E, Hasler U - Physiol Rep (2014)

Bottom Line: Hyperosmotic stress profoundly challenges cellular homeostasis and induces endoplasmic reticulum (ER) stress.Both hyperosmolality and chemical induction of ER stress decreased ENaC expression in vitro.ENaC depletion by either stimulus was abolished by transcriptional inhibition and by the chemical chaperone 4-phenylbutyric acid and was partly abrogated by either PERK or ATF6 silencing.

View Article: PubMed Central - PubMed

Affiliation: UPMC/INSERM/Paris Descartes U1138 CNRS ERL 8228, Equipe 3 Métabolisme et Physiologie Rénale, Centre de Recherche des Cordeliers, Paris, France.

No MeSH data available.


Related in: MedlinePlus

Hyperosmolality decreases ENaC abundance. (A) Q‐PCR analysis of ENaC and AQP2 mRNA abundance of microdissected CCD and OMCD from mice that were deprived of water for 24 h (WD) or given free access to water (Ctl). Data is represented as fold difference of expression over values obtained in CCD of Ctl homogenate and is expressed as the mean ± SEM of data from at least six animals. (B, C and E) mRNA abundance of ENaC (B and C) and AQP2 (E) in mCCDcl1 (B and E) and mpkCCDcl4 (C and E) cells challenged or not (Ctl) with NaCl or urea (500 mOsmol/kg) for 1–24 h. (D) Western blot against ENaCα from lysate of mCCDcl1 (top panel) and mpkCCDcl4 (bottom panel) cells challenged 6 or 24 h with aldosterone (1 μmol/L) or 1–24 h with NaCl (500 mOsmol/kg). The blot against ENaCα at right was overexposed in order to better illustrate decreased ENaCα abundance by NaCl. β‐actin was used as a loading control. For (B), (C) and (E), data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of four independent experiments.
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fig01: Hyperosmolality decreases ENaC abundance. (A) Q‐PCR analysis of ENaC and AQP2 mRNA abundance of microdissected CCD and OMCD from mice that were deprived of water for 24 h (WD) or given free access to water (Ctl). Data is represented as fold difference of expression over values obtained in CCD of Ctl homogenate and is expressed as the mean ± SEM of data from at least six animals. (B, C and E) mRNA abundance of ENaC (B and C) and AQP2 (E) in mCCDcl1 (B and E) and mpkCCDcl4 (C and E) cells challenged or not (Ctl) with NaCl or urea (500 mOsmol/kg) for 1–24 h. (D) Western blot against ENaCα from lysate of mCCDcl1 (top panel) and mpkCCDcl4 (bottom panel) cells challenged 6 or 24 h with aldosterone (1 μmol/L) or 1–24 h with NaCl (500 mOsmol/kg). The blot against ENaCα at right was overexposed in order to better illustrate decreased ENaCα abundance by NaCl. β‐actin was used as a loading control. For (B), (C) and (E), data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of four independent experiments.

Mentions: Water deprivation increases plasma AVP concentration and consequently increases extracellular osmolality of the medulla but not cortex. We examined in vivo whether hyperosmolality affects ENaC mRNA expression by comparing cortical and medullary ENaC expression from microdissected CCD and OMCD of animals that were deprived of water for 24 h or given free access to water. We also compared changes of ENaC expression to those of AQP2. As previously reported (Kishore et al. 1996), AQP2 abundance in both CCD and OMCD was greatest in water‐deprived animals as compared to normally hydrated animals (Fig. 1A). Contrary to AQP2, dehydration decreased mRNA expression of all three ENaC subunits, but only in OMCD. In CCD, expression levels of all three ENaC subunits increased (Fig. 1A).


Epithelial sodium channel abundance is decreased by an unfolded protein response induced by hyperosmolality.

Crambert G, Ernandez T, Lamouroux C, Roth I, Dizin E, Martin PY, Féraille E, Hasler U - Physiol Rep (2014)

Hyperosmolality decreases ENaC abundance. (A) Q‐PCR analysis of ENaC and AQP2 mRNA abundance of microdissected CCD and OMCD from mice that were deprived of water for 24 h (WD) or given free access to water (Ctl). Data is represented as fold difference of expression over values obtained in CCD of Ctl homogenate and is expressed as the mean ± SEM of data from at least six animals. (B, C and E) mRNA abundance of ENaC (B and C) and AQP2 (E) in mCCDcl1 (B and E) and mpkCCDcl4 (C and E) cells challenged or not (Ctl) with NaCl or urea (500 mOsmol/kg) for 1–24 h. (D) Western blot against ENaCα from lysate of mCCDcl1 (top panel) and mpkCCDcl4 (bottom panel) cells challenged 6 or 24 h with aldosterone (1 μmol/L) or 1–24 h with NaCl (500 mOsmol/kg). The blot against ENaCα at right was overexposed in order to better illustrate decreased ENaCα abundance by NaCl. β‐actin was used as a loading control. For (B), (C) and (E), data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of four independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255800&req=5

fig01: Hyperosmolality decreases ENaC abundance. (A) Q‐PCR analysis of ENaC and AQP2 mRNA abundance of microdissected CCD and OMCD from mice that were deprived of water for 24 h (WD) or given free access to water (Ctl). Data is represented as fold difference of expression over values obtained in CCD of Ctl homogenate and is expressed as the mean ± SEM of data from at least six animals. (B, C and E) mRNA abundance of ENaC (B and C) and AQP2 (E) in mCCDcl1 (B and E) and mpkCCDcl4 (C and E) cells challenged or not (Ctl) with NaCl or urea (500 mOsmol/kg) for 1–24 h. (D) Western blot against ENaCα from lysate of mCCDcl1 (top panel) and mpkCCDcl4 (bottom panel) cells challenged 6 or 24 h with aldosterone (1 μmol/L) or 1–24 h with NaCl (500 mOsmol/kg). The blot against ENaCα at right was overexposed in order to better illustrate decreased ENaCα abundance by NaCl. β‐actin was used as a loading control. For (B), (C) and (E), data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of four independent experiments.
Mentions: Water deprivation increases plasma AVP concentration and consequently increases extracellular osmolality of the medulla but not cortex. We examined in vivo whether hyperosmolality affects ENaC mRNA expression by comparing cortical and medullary ENaC expression from microdissected CCD and OMCD of animals that were deprived of water for 24 h or given free access to water. We also compared changes of ENaC expression to those of AQP2. As previously reported (Kishore et al. 1996), AQP2 abundance in both CCD and OMCD was greatest in water‐deprived animals as compared to normally hydrated animals (Fig. 1A). Contrary to AQP2, dehydration decreased mRNA expression of all three ENaC subunits, but only in OMCD. In CCD, expression levels of all three ENaC subunits increased (Fig. 1A).

Bottom Line: Hyperosmotic stress profoundly challenges cellular homeostasis and induces endoplasmic reticulum (ER) stress.Both hyperosmolality and chemical induction of ER stress decreased ENaC expression in vitro.ENaC depletion by either stimulus was abolished by transcriptional inhibition and by the chemical chaperone 4-phenylbutyric acid and was partly abrogated by either PERK or ATF6 silencing.

View Article: PubMed Central - PubMed

Affiliation: UPMC/INSERM/Paris Descartes U1138 CNRS ERL 8228, Equipe 3 Métabolisme et Physiologie Rénale, Centre de Recherche des Cordeliers, Paris, France.

No MeSH data available.


Related in: MedlinePlus