Short-chain fatty acids reduce expression of specific protein kinase C isoforms in human colonic epithelial cells.
LIM1215 colon cancer cells were used as a model of human colonic epithelium to examine the effects of butyrate on protein kinase C (PKC) activity and isoform expression. On Western blot analysis, LIM1215 cells express the PKC isoforms alpha, beta, epsilon, zeta, and lambda, but not gamma, straight theta, or micro. Treatment with 2 mM butyrate for 48 h reduced cellular PKC activity up to 50% and specifically reduced the expression of PKC alpha and PKC epsilon. Similar results were obtained using Caco-2 colon cancer cells. These effects were neither a consequence of the induction of differentiation itself nor the result of direct or indirect activation of PKC. Although dependent on gene transcription and protein synthesis, the effect was not due to a reduction in the synthesis of PKC protein. Butyrate's effect was independent of its beta-oxidation but was mimicked, at least in part, by trichostatin A, an inhibitor of histone deacetylase.
Rickard
K L
KL
Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
Gibson
P R
PR
Wilson
N J
NJ
Mariadason
J M
JM
Phillips
W A
WA
D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation; D005232:Fatty Acids, Volatile / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology
D002087:Butyrates; D005232:Fatty Acids, Volatile; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D011500:Protein Synthesis Inhibitors; D011493:Protein Kinase C