Document Detail

Specific modulation of intestinal epithelial brush border enzyme expression by a phorbol ester.
MedLine Citation:
PMID:  7630114     Owner:  NLM     Status:  MEDLINE    
Much is known about intestinal epithelial regulation by growth factors and nutrients but the intracellular signals governing cell phenotype are less well understood. In an initial attempt to evaluate the role of protein kinase C in these events, we studied the effects of protein kinase C modulation by the phorbol ester TPA upon the differentiation, motility, and doubling time of the human intestinal epithelial Caco-2 cell line, a common model for enterocytic brush border enzyme expression. We also compared the effects of TPA to those of 4 alpha-phorbol 12,13-didecanoate, which does not modulate protein kinase C activity. Differentiation was studied by quantitating brush order dipeptidyl peptidase (DPDD)-specific activity in protein-matched Caco-2 lysates via synthetic substrate digestion. Alkaline phosphatase (AP) was studied for comparison. Doubling time was assessed by log transformation of serial cell counts and motility by monolayer expansion across type I collagen. TPA (0.03-0.7 micrograms/ml) dose-dependently stimulated DPDD, with a maximal 455 +/- 26% increase at 0.7 micrograms/ml (P < 0.01, n = 5). However, TPA dose-dependently inhibited AP to a maximal 91.6 +/- 0.3% decrease (P < 0.01, n = 5). TPA also dose-dependently prolonged the cell doubling time from 26.5 +/- 0.4 to 64.5 +/- 8.8 hr (n = 20, P < 0.01) with a maximal effect at 1.0 micrograms/ml and inhibited migration with essentially complete ablation of cell motility at 0.1 micrograms/ml (n = 10, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
M D Basson; F Hong; N J Emenaker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of surgical research     Volume:  59     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1995-09-05     Completed Date:  1995-09-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  121-6     Citation Subset:  IM    
Department of Surgery, Yale University, New Haven, Connecticut, USA.
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MeSH Terms
Alkaline Phosphatase / metabolism
Cell Line
Cell Movement
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
Dose-Response Relationship, Drug
Intestines / cytology,  enzymology*
Microvilli / enzymology
Phorbol Esters / pharmacology
Protein Kinase C / physiology*
Signal Transduction
Tetradecanoylphorbol Acetate / pharmacology*
Reg. No./Substance:
0/Phorbol Esters; 16561-29-8/Tetradecanoylphorbol Acetate; 24928-17-4/phorbol-12,13-didecanoate; EC Kinase C; EC Phosphatase; EC 3.4.14.-/Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

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