Dietary fish oil blocks carcinogen-induced down-regulation of colonic protein kinase C isozymes.
In order to elucidate the influence of dietary constituents on colonic intracellular signal transduction, the effect of different fats on rat colonic epithelial protein kinase C (PKC) alpha (classical), delta (novel) and lambda-zeta (atypical) expression was determined in carcinogen-treated animals. Sprague-Dawley rats were provided with one of two fats (corn oil and fish oil); plus or minus the carcinogen azoxymethane (AOM) and killed at two time points (15 and 37 weeks) in a 2x2x2 factorial design. At 5 and 6 weeks of age, animals were injected s.c. with either AOM at a dose of 15 mg/kg body weight or saline once a week for 2 weeks and continued on the same diet until termination of the study. At 15 and 37 weeks after the second injection, 10 rats from each treatment group were killed. Colonic PKC alpha, delta and lambda-zeta steady-state protein and mRNA levels were determined using immunoblotting and relative quantitative polymerase chain reaction, respectively. Colonic mucosa from rats injected with AOM had significantly suppressed membrane and cytosolic PKC alpha and cytosolic lambda-zeta protein levels (P < 0.05) as compared to saline-injected control animals at both time points. In contrast, rats fed fish oil diets had significantly higher (P < 0.05) cytosolic PKC delta and lambda-zeta protein levels relative to animals fed corn oil diets. However, the effect of diet and AOM on the steady-state expression of PKC alpha, delta and zeta mRNA was not consistent with changes in the respective isozyme protein levels, suggesting regulation at the post-transcriptional level. These data demonstrate that dietary fish oil blocks the carcinogen-induced decrease in the steady-state levels of colonic mucosal PKC delta and lambda-zeta, which may in part explain why this fat source protects against colon cancer development.
Jiang
Y H
YH
Faculty of Nutrition, Molecular and Cell Biology Group, Texas A&M University, College Station 77843-2471, USA.
Lupton
J R
JR
Chapkin
R S
RS
D000818:Animals; D001397:Azoxymethane / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000201:enzymology; D003314:Corn Oil / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005395:Fish Oils / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D007527:Isoenzymes; D003314:Corn Oil; D011493:Protein Kinase C; D001397:Azoxymethane