Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation and reactive oxygen formation by bile acids

• Published in: The Journal of clinical investigation Vol. 79; no. 2; pp. 532 - 541
• Main Authors: Craven, P A, Pfanstiel, J, DeRubertis, F R
• Format: Journal Article
• Language: English
• Published: United States 01-02-1987
• Subjects: Animals; Cell Division - drug effects; Chenodeoxycholic Acid - pharmacology; Colon - cytology; Colon - drug effects; Colon - metabolism; Cytochrome c Group - metabolism; Deoxycholic Acid - pharmacology; Enzyme Activation; Epithelial Cells; Epithelium - drug effects; Epithelium - metabolism; Female; Kinetics; Luminescent Measurements; Oxygen; Phorbol Esters - pharmacology; Protein Kinase C - isolation & purification; Protein Kinase C - metabolism; Rats; Rats, Inbred Strains; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0021-9738
• DOI: 10.1172/jci112844

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.