| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 82 === Butyrate, a four carbone fatty acid, has been shown to induce
differentiation and inhibit proliferation in many cell lines.
But the cellular mechanism is still not known. In primary
culture of rabbit proximal tubular cells(PT cells), butyrate
upregultes the activities of differentiation marker enzymes
such as leucine aminopeptidase (LAP), sodium dependent glucose
trans- porter, and gluconeogenic enzyme phosphoenoylpyruvate
carboxy- kinase (PEPCK). We previously found that butyrate
inhibited proliferation of PT cells, but unexpectedly,
decreased activity, protein abundance and gene expression of Na,
K-ATPase. TGF-beta, a potent growth and differentiation agent
for epithelial cells, was then selected to studywhether it has
same effects with butyrate in cultured proximal cells.
treatment of TGF-beta(0.5- 5 ng/ml) also decreases Na,K-ATPase
activity. Na,K-ATPase alpha and beta protein and mRNA abundance
was also decreased by TGF- beta incubation, suggesting that TGF-
beta induced decrease of Na,K-ATPase may be via a
pretranslational mechanism. The time course study of TGF-beta
and butyrate to decrease Na,K-ATPase activity and alpha and
beta protein and mRNA abundance revealed that the effect of TGF-
beta preceded the effect of butyrate. Moreover, treatment of
cycloheximide(20 ug/ml) inhibited butyrate -induced inhibition
of Na,K-ATPase gene expression. However, treatment with
cycloheximide could not block TGF-beta-induced inhibition of Na,
K-ATPase gene expression. In addition, butyrate fails to induce
TGF-beta gene expression and anti-TGF-beta 1 antibody cannot
block the inhibitory effect of butyrate on thymidine
incorporation in cultured proximal tubular cells. These data
suggest that TGF-beta can mimicks the effect of butyrate on
cell proliferation and Na,K-ATPase of proximal tubular cells,
but is not the mediator of butyrate.
|
|---|
