Tyrosine kinase inhibitors reverse butyrate stimulation of human Caco-2 intestinal epithelial cell alkaline phosphatase but not butyrate promotion of dipeptidyl dipeptidase.
Short chain fatty acids such as sodium butyrate are concentrated in the colonic lumen and may protect against colon carcinogenesis by maintaining colonocytic differentiation, but the mechanisms by which they act are not fully understood. It has recently been suggested that short chain fatty acids modulate cellular tyrosine kinase activity in addition to altering chromatin structure via regulation of histone acetylation and DNA methylation. Therefore, the authors evaluated the influence of tyrosine kinase inhibition on the effects of 10 mM butyrate on human Caco-2 intestinal epithelial differentiation, using alkaline phosphatase and dipeptidyl dipeptidase specific activity as markers of differentiation, and two tyrosine kinase inhibitors, of different mechanisms of action and different effects on Caco-2 brush border enzyme specific activity, to block tyrosine kinase activity. As expected, butyrate stimulated both alkaline phosphatase and dipeptidyl dipeptidase specific activity. The tyrosine kinase inhibitors prevented, and indeed one inhibitor reversed the effects of butyrate on alkaline phosphatase specific activity. However, tyrosine kinase inhibition did not prevent butyrate stimulation of dipeptidyl dipeptidase specific activity. Different pathways are likely to regulate the effects of butyrate on expression of these two brush border enzymes. Butyrate stimulation of alkaline phosphatase, but not dipeptidyl dipeptidase, may involve tyrosine phosphorylation signaling.
Basson
M D
MD
Departments of Surgery, Yale University School of Medicine and CT VA Health Care System, 333 Cedar Street, New Haven, CT 06520-8062, USA.
Hong
F
F
D000230:Adenocarcinoma; D000469:Alkaline Phosphatase / Q000378:metabolism*; D002087:Butyrates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D002087:Butyrates; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000469:Alkaline Phosphatase; C048212:erbstatin