Carcinogenesis, Vol 18, 351-357, Copyright © 1997 by Oxford University Press
YH Jiang, JR Lupton and RS Chapkin
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.
ARTICLES
Dietary fish oil blocks carcinogen-induced down-regulation of colonic protein kinase C isozymes
Faculty of Nutrition, Molecular and Cell Biology Group, Texas A&M University, College Station 77843-2471, USA.
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