Role of protein kinase C and transcription factor AP-1 in the acid-induced increase in Na/H antiporter activity.
Chronic incubation of cultured renal tubular epithelial cells in acid medium causes an increase in Na/H antiporter activity that persists after removal from acid, is dependent on protein synthesis, and is associated with an increase in Na/H antiporter mRNA. Chronic activation of protein kinase C has similar effects in these cells. The present studies examined the role of protein kinase C in the effect of acid incubation. Incubation of MCT cells in acid for 24 h caused a 50% increase in Na/H antiporter activity. This was prevented by inhibition of protein kinase C, either with sphingosine or by protein kinase C downregulation. Pertussis toxin pretreatment did not prevent the increase in antiporter activity. Acid incubation caused an increase in transcription factor AP-1 activity, as shown by an increase in expression from a reporter gene containing six tandem AP-1 binding sites. This was associated with transient increases in c-fos and c-jun mRNAs. This response is typical of that for gene activation by protein kinase C. These studies demonstrate that acid activation of the Na/H antiporter requires protein kinase C and is associated with c-fos and c-jun expression and increased AP-1 activity.
Horie
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S
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Moe
O
O
Yamaji
Y
Y
Cano
A
A
Miller
R T
RT
Alpern
R J
RJ
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D016762:Genes, fos; D016758:Genes, jun; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal; D007700:Kinetics; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D017923:Sodium-Hydrogen Exchangers; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection
D002352:Carrier Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate