Document Detail

Modulation of Na+ transport and epithelial sodium channel expression by protein kinase C in rat alveolar epithelial cells.
MedLine Citation:
PMID:  16391706     Owner:  NLM     Status:  MEDLINE    
Although the amiloride-sensitive epithelial sodium channel (ENaC) plays an important role in the modulation of alveolar liquid clearance, the precise mechanism of its regulation in alveolar epithelial cells is still under investigation. Protein kinase C (PKC) has been shown to alter ENaC expression and activity in renal epithelial cells, but much less is known about its role in alveolar epithelial cells. The objective of this study was to determine whether PKC activation modulates ENaC expression and transepithelial Na+ transport in cultured rat alveolar epithelial cells. Alveolar type II cells were isolated and cultured for 3 to 4 d before they were stimulated with phorbol 12-myristate 13-acetate (PMA 100 nmol/L) for 4 to 24 h. PMA treatment significantly decreased alpha, beta, and gammaENaC expression in a time-dependent manner, whereas an inactive form of phorbol ester had no apparent effect. This inhibitory action was seen with only 5-min exposure to PMA, which suggested that PKC activation was very important for the reduction of alphaENaC expression. The PKC inhibitors bisindolylmaleimide at 2 micromol/L and Gö6976 at 2 micromol/L diminished the PMA-induced suppression of alphaENaC expression, while rottlerin at 1 micromol/L had no effect. PMA elicited a decrease in total and amiloride-sensitive current across alveolar epithelial cell monolayers. This decline in amiloride-sensitive current was not blocked by PKC inhibitors except for a partial inhibition with bisindolylmaleimide. PMA induced a decrease in rubidium uptake, indicating potential Na+-K+-ATPase inhibition. However, since ouabain-sensitive current in apically permeabilized epithelial cells was similar in PMA-treated and control cells, the inhibition was most probably related to reduced Na+ entry at the apical surface of the cells. We conclude that PKC activation modulates ENaC expression and probably ENaC activity in alveolar epithelial cells. Ca2+-dependent PKC is potentially involved in this response.
Toshiyuki Yamagata; Yuko Yamagata; Chantal Massé; Marie-Claude Tessier; Emmanuelle Brochiero; André Dagenais; Yves Berthiaume
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  83     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2006-01-04     Completed Date:  2006-05-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  977-87     Citation Subset:  IM    
Département de médecine, Centre de recherche, Centre hospitalier de l'Université de Montréal Hôtel-Dieu, Montreal, QC, Canada.
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MeSH Terms
Amiloride / pharmacology
Biological Transport
Cells, Cultured
Enzyme Inhibitors / pharmacology
Epithelial Cells / drug effects*,  physiology
Epithelial Sodium Channel
Gene Expression Regulation
Protein Kinase C / antagonists & inhibitors,  metabolism*
Pulmonary Alveoli / cytology,  drug effects,  physiology
Rats, Sprague-Dawley
Rubidium Radioisotopes / metabolism
Sodium / metabolism
Sodium Channel Blockers / pharmacology
Sodium Channels / genetics,  metabolism*
Sodium-Potassium-Exchanging ATPase / genetics,  metabolism
Tetradecanoylphorbol Acetate / pharmacology*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Epithelial Sodium Channel; 0/Rubidium Radioisotopes; 0/Sodium Channel Blockers; 0/Sodium Channels; 16561-29-8/Tetradecanoylphorbol Acetate; 2609-46-3/Amiloride; 7440-23-5/Sodium; EC Kinase C; EC ATPase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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