Limits...
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

NaCl dose‐dependence and effects of aldosterone and TonEBP on decreased ENaC abundance by NaCl. (A and B) mRNA abundance of ENaC in mCCDcl1 (A) and mpkCCDcl4 (B) cells challenged or not (Ctl) 6 h with NaCl (350–500 mOsmol/kg). (C) mRNA abundance of ENaC in mCCDcl1 cells challenged or not (Ctl) with aldosterone (1 μmol/L) or NaCl (500 mOsmol/kg) alone or with both stimuli for 6 h. Data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of three independent experiments. (D) mCCDcl1 cells transfected with scramble siRNA or siRNA against TonEBP (siTonEBP) were challenged or not (Ctl) with NaCl for 6 h. TonEBP, aldose reductase (AR) and ENaC mRNA abundance was analyzed by Q‐PCR. Data is represented as fold difference over non‐stimulated cells transfected with scramble siRNA and is expressed as the mean ± SEM of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4255800&req=5

fig02: NaCl dose‐dependence and effects of aldosterone and TonEBP on decreased ENaC abundance by NaCl. (A and B) mRNA abundance of ENaC in mCCDcl1 (A) and mpkCCDcl4 (B) cells challenged or not (Ctl) 6 h with NaCl (350–500 mOsmol/kg). (C) mRNA abundance of ENaC in mCCDcl1 cells challenged or not (Ctl) with aldosterone (1 μmol/L) or NaCl (500 mOsmol/kg) alone or with both stimuli for 6 h. Data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of three independent experiments. (D) mCCDcl1 cells transfected with scramble siRNA or siRNA against TonEBP (siTonEBP) were challenged or not (Ctl) with NaCl for 6 h. TonEBP, aldose reductase (AR) and ENaC mRNA abundance was analyzed by Q‐PCR. Data is represented as fold difference over non‐stimulated cells transfected with scramble siRNA and is expressed as the mean ± SEM of three independent experiments.

Mentions: Addition of NaCl to the cell medium decreased ENaC mRNA expression in a dose‐dependent manner in both mCCDcl1 (Fig. 2A) and mpkCCDcl4 (Fig. 2B) cells, with a maximal effect observed at 500 mOsmol/kg. We investigated the effects of aldosterone on decreased ENaC mRNA abundance by hyperosmolality. ENaCα, but not ENaCβ or ENaCγ, was increased by aldosterone alone and NaCl decreased expression of each ENaC subunit in the absence or presence of aldosterone (Fig. 2C). This indicates that hyperosmolality decreases ENaC abundance independently of aldosterone.


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)

NaCl dose‐dependence and effects of aldosterone and TonEBP on decreased ENaC abundance by NaCl. (A and B) mRNA abundance of ENaC in mCCDcl1 (A) and mpkCCDcl4 (B) cells challenged or not (Ctl) 6 h with NaCl (350–500 mOsmol/kg). (C) mRNA abundance of ENaC in mCCDcl1 cells challenged or not (Ctl) with aldosterone (1 μmol/L) or NaCl (500 mOsmol/kg) alone or with both stimuli for 6 h. Data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of three independent experiments. (D) mCCDcl1 cells transfected with scramble siRNA or siRNA against TonEBP (siTonEBP) were challenged or not (Ctl) with NaCl for 6 h. TonEBP, aldose reductase (AR) and ENaC mRNA abundance was analyzed by Q‐PCR. Data is represented as fold difference over non‐stimulated cells transfected with scramble siRNA and is expressed as the mean ± SEM of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: NaCl dose‐dependence and effects of aldosterone and TonEBP on decreased ENaC abundance by NaCl. (A and B) mRNA abundance of ENaC in mCCDcl1 (A) and mpkCCDcl4 (B) cells challenged or not (Ctl) 6 h with NaCl (350–500 mOsmol/kg). (C) mRNA abundance of ENaC in mCCDcl1 cells challenged or not (Ctl) with aldosterone (1 μmol/L) or NaCl (500 mOsmol/kg) alone or with both stimuli for 6 h. Data is represented as fold difference over non‐stimulated cells and is expressed as the mean ± SEM of three independent experiments. (D) mCCDcl1 cells transfected with scramble siRNA or siRNA against TonEBP (siTonEBP) were challenged or not (Ctl) with NaCl for 6 h. TonEBP, aldose reductase (AR) and ENaC mRNA abundance was analyzed by Q‐PCR. Data is represented as fold difference over non‐stimulated cells transfected with scramble siRNA and is expressed as the mean ± SEM of three independent experiments.
Mentions: Addition of NaCl to the cell medium decreased ENaC mRNA expression in a dose‐dependent manner in both mCCDcl1 (Fig. 2A) and mpkCCDcl4 (Fig. 2B) cells, with a maximal effect observed at 500 mOsmol/kg. We investigated the effects of aldosterone on decreased ENaC mRNA abundance by hyperosmolality. ENaCα, but not ENaCβ or ENaCγ, was increased by aldosterone alone and NaCl decreased expression of each ENaC subunit in the absence or presence of aldosterone (Fig. 2C). This indicates that hyperosmolality decreases ENaC abundance independently of aldosterone.

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