Cycloheximide increases glucocorticoid-stimulated alpha -ENaC mRNA in collecting duct cells by p38 MAPK-dependent pathway

Omar A Itani; Kristyn L Cornish; Kang Z Liu; Christie P Thomas

doi:10.1152/ajprenal.00088.2002

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Cycloheximide increases glucocorticoid-stimulated alpha -ENaC mRNA in collecting duct cells by p38 MAPK-dependent pathway

Journal article

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Cycloheximide increases glucocorticoid-stimulated alpha -ENaC mRNA in collecting duct cells by p38 MAPK-dependent pathway

Omar A Itani, Kristyn L Cornish, Kang Z Liu and Christie P Thomas

American journal of physiology. Renal physiology, Vol.284(4), pp.F778-787

04/2003

DOI: 10.1152/ajprenal.00088.2002

PMID: 12505861

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Abstract

Aldosterone and glucocorticoids (GCs) stimulate Na(+) reabsorption in the collecting ducts by increasing the activity of the epithelial Na(+) channel (ENaC). Our laboratory has used Madin-Darby canine kidney-C7 cells to demonstrate that this effect is associated with an increase in alpha-ENaC gene transcription (Mick VE, Itani OA, Loftus RW, Husted RF, Schmidt TJ, and Thomas CP, Mol Endocrinol 15: 575-588, 2001). Cycloheximide (CHX) superinduced the GC-stimulated alpha-ENaC expression in a dose-dependent manner, but had no effect on basal or aldosterone-stimulated alpha-ENaC expression, whereas anisomycin inhibited basal and corticosteroid-stimulated alpha-ENaC expression. The superinduction of alpha-ENaC expression was also seen with hypotonicity, was blocked by RU-38486, and was independent of protein synthesis. CHX had no effect on alpha-ENaC mRNA half-life, confirming that its effect was via an increase in alpha-ENaC transcription. The effect of CHX and hypotonicity on alpha-ENaC expression was abolished by SB-202190, indicating an effect mediated via p38 MAPK. Consistent with this scheme, CHX increased pp38 and MKK6, an upstream activator of p38, stimulated alpha-ENaC promoter activity. These data confirm a model in which CHX activates p38 in Madin-Darby canine kidney-C7 cells to increase alpha-ENaC gene transcription in a GC-dependent manner.

Enzyme Activators - pharmacology

Gene Expression - drug effects

Emetine - pharmacology

Hypotonic Solutions - pharmacology

Kidney Tubules, Collecting - cytology

RNA, Messenger - metabolism

Epithelial Sodium Channels

Dexamethasone - pharmacology

Sodium Channels - metabolism

Protein Synthesis Inhibitors - pharmacology

p38 Mitogen-Activated Protein Kinases

Kidney Tubules, Collecting - drug effects

Cell Line

Enzyme Inhibitors - pharmacology

Aldosterone - pharmacology

Cycloheximide - pharmacology

Kidney Tubules, Collecting - metabolism

Animals

Glucocorticoids - antagonists & inhibitors

Mitogen-Activated Protein Kinases - antagonists & inhibitors

Dogs

Glucocorticoids - pharmacology

Signal Transduction - physiology

Sodium Channels - genetics

Mifepristone - pharmacology

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: Cycloheximide increases glucocorticoid-stimulated alpha -ENaC mRNA in collecting duct cells by p38 MAPK-dependent pathway
Creators: Omar A Itani - Department of Internal Medicine, and Graduate Program in Molecular Biology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
Kristyn L Cornish
Kang Z Liu
Christie P Thomas
Resource Type: Journal article
Publication Details: American journal of physiology. Renal physiology, Vol.284(4), pp.F778-787
DOI: 10.1152/ajprenal.00088.2002
PMID: 12505861
NLM abbreviation: Am J Physiol Renal Physiol
ISSN: 1931-857X
eISSN: 1522-1466
Publisher: United States
Grant note: R01 DK054348 / NIDDK NIH HHS DK54348 / NIDDK NIH HHS
Language: English
Date published: 04/2003
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Nephrology; Internal Medicine
Record Identifier: 9983986259702771

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