Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation and reactive oxygen formation by bile acids.
Deoxycholate (DOC), chenodeoxycholate, 12-O-tetradecanoyl phorbol-13-acetate (TPA), or 1-oleoyl-2-acetyl-glycerol (OAG) activated colonic epithelial protein kinase C as reflected by translocation from the soluble to the particulate cell fraction. Activation of protein kinase C was correlated with stimulation of enhanced proliferative activity of colonic mucosa and reactive oxygen production. TPA and OAG, but not DOC, directly activated soluble protein kinase C in vitro. However, DOC rapidly increased labeled inositol phosphate and diacylglycerol accumulation in colonic epithelial cells. Retinoic acid inhibited protein kinase C activity and suppressed DOC-, TPA-, and OAG-induced increases in reactive oxygen production. The results support a role for protein kinase C in the stimulation of colonic epithelial proliferative activity and reactive oxygen production induced by bile acids, TPA and OAG. In contrast to TPA and OAG, which activate protein kinase C directly, bile acids appear to activate protein kinase C indirectly by increasing the diacylglycerol content of colonic epithelium.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004789:Enzyme Activation; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008163:Luminescent Measurements; D010100:Oxygen; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003574:Cytochrome c Group; D010703:Phorbol Esters; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen