Effects of specific bile acids on c-fos messenger RNA levels in human colon carcinoma Caco-2 cells
Effects of specific bile acids on c-fos messenger RNA levels in human colon carcinoma Caco-2 cells
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DOI：
10.1016/s0928-0987(00)00111-1
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发表时间：
2000-10-01
影响因子：
4.6
通讯作者：
Spampinato, S
中科院分区：
文献类型：
--
作者：
Di Toro, R;Campana, G;Spampinato, S
胆汁酸可能通过激活控制细胞增殖的信号通路以及其他细胞系统，在肠道炎症的发病机制中发挥作用。我们研究了不同胆酸，特别是鹅去氧胆酸（CDCA）和熊去氧胆酸（UDCA）对结肠癌Caco-2细胞中参与细胞增殖和分化调节的原癌基因c-fos的稳态和转录调控的作用。特异性胆汁酸对c- somrna的表达有刺激作用。这被证明是浓度和时间依赖的，可能部分是由于相应基因转录速率的增加，而不是mRNA稳定性的任何变化。在Caco-2细胞中，暴露于250 muM CDCA 1 h， c-Sos mRNA最大增加（约为对照的2.5倍诱导）；脱氧胆酸（DCA; 250 muM）和石胆酸（LCA; 250 muM）的效果较差（大约是对照组的2倍）。UDCA和胆酸（CA）对该细胞系c-Sos基因表达无影响。最后，我们研究了蛋白激酶C （PKC）在胆汁酸对C -fos基因转录调控中的作用。虽然12- o -十四烷酰13-乙酸酯（10 nM）诱导的c-fos被双吲哚基马来酰亚胺I （1 muM）完全拮抗；只有约40%的胆汁酸介导的c-fos mRNA升高被阻断。因此，PKC以及其他信号通路参与了CDCA-、DCA-和lca诱导的c-Sos基因表达。(C) 2000 Elsevier Science B.V.版权所有
Bile acids may play a role in the pathogenesis of intestinal inflammation by activating the signalling pathways that control cell proliferation, among other cell systems. We investigated the action of different bile acids, particularly chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), on steady-state and transcriptional regulation of the protooncogene c-fos, involved in the regulation of cell proliferation and differentiation, in colon carcinoma Caco-2 cells. Specific bile acids had a stimulatory effect of on the expression of c-Sos mRNA. This proved to be concentration- and time-dependent and may be partly due to an increase in the rate of transcription of the corresponding gene rather than to any change in the stability of mRNA. In Caco-2 cells exposed to 250 muM CDCA for 1 h a maximal increase of c-Sos mRNA (approximate to2.5-fold induction over the control) was observed; deoxycholic acid (DCA; 250 muM) and lithocholic acid (LCA; 250 muM) were less effective (approximate to2-fold induction over the control). UDCA and cholic acid (CA) did not modify c-Sos gene expression in this cell line. Finally, we investigated the role of protein kinase C (PKC) in transcriptional regulation of the c-fos gene by bile acids. Although induction of c-fos by 12-O-tetradecanoyl 13-acetate (10 nM), a potent PKC activator, was completely antagonised by bis-indolyl-maleimide I (1 muM); only about 40% of the bile acid-mediated rise in c-fos mRNA was blocked. Thus it appears that PKC, as well as other signalling pathways, is involved in CDCA-, DCA- and LCA-induced c-Sos gene expression. (C) 2000 Elsevier Science B.V. All rights reserved.