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, theta or m u. Treatment with 2 mM butyrate for 48 h reduced cellular PKC activity up t o 50% and specifically reduced the expression of PKC alpha and PKC epsilon. Similar were obtained using Caco-2 colon cancer cells. These effects were neither a consequence of the induction of differentiation itself nor the re sult of direct or indirect activation of PKC. Although dependent on gene tr anscription and protein synthesis, the effect was not due to a reduction in the synthesis of PKC protein. Butyrate's effect was independent of its bet a-oxidation but was mimicked, at least in part, by trichostatin A, an inhib itor of histone deacetylase. (C) 2000 Wiley-Liss, Inc.