Roleofprotein kinase C andtranscription factor AP-1inthe acid-induced increase inNa/Hantiporter activity

Chronic incubation ofcultured renal tubular epithelial cells inacidmediumcauses anincrease inNa/H antiporter activity thatpersists after removal fromacid, is dependent onprotein synthesis, andisassociated withan increase inNa/Hantiporter mRNA.Chronic activation of protein kinase C hassimilar effects inthese cells. Thepresent studies examined therole ofprotein kinase Cintheeffect ofacid incubation. Incubation ofMCT cells inacid for24hcaused a 50%increase inNa/Hantiporter activity. Thiswasprevented byinhibition ofprotein kinase C,either withsphingosine orby protein kinase Cdownregulation. Pertussis toxin pretreatment didnotprevent theincrease inantiporter activity. Acidincu- bation caused anincrease intranscription factor AP-1activity, asshownbyanincrease inexpression fromareporter gene containing sixtandem AP-1binding sites. Thiswasassociated withtransient increases inc-fos andc-jun mRNAs.Thisre- sponse istypical ofthat forgeneactivation byprotein kinase C. Thesestudies demonstrate thatacidactivation oftheNa/H antiporter requires protein kinase Candisassociated withc-fos