Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.
Short-chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cells.
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DOI：
10.1053/gast.2001.27028
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发表时间：
2001-09
期刊：
影响因子：
29.4
通讯作者：
H. Ren;M. Musch;K. Kojima;D. Boone;A. Ma;E. Chang
中科院分区：
文献类型：
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作者：
H. Ren;M. Musch;K. Kojima;D. Boone;A. Ma;E. Chang
背景与目的由于短链脂肪酸(SCFAs)和热休克蛋白(HSPs)对肠上皮细胞(IECs)具有保护作用，我们研究了SCFAs对IEC HSP表达的调节作用。方法采用免疫印迹和免疫组织化学方法检测HSP25、HSP72和hsc73蛋白在大鼠肠组织和IEC-18细胞中的表达。用~(51)Cr释放法检测HSP25反义和正义表达HSP25的细胞在氧化应激(一氯胺)条件下的细胞存活率。结果丁酸诱导大鼠IEC-18细胞HSP25蛋白表达呈时间和浓度依赖性增加，对HSP72和hsc73无影响，但对3T3成纤维细胞无影响。其他单链脂肪酸，包括代谢不良的异丁酸，也诱导了HSP25的选择性表达。丁酸处理显著提高了IEC-18细胞抵抗氧化剂(一氯胺)损伤的能力。在丁酸盐诱导的HSP25被稳定的HSP25反义转染阻断的细胞中，这种作用可以被阻断。此外，过表达HSP25的IEC-18细胞对一氯胺的抗性增强。在体内，增加膳食纤维增加了结肠的HSP25，但不增加回肠近端的HSP25，而对HSP72或hsc73的表达没有影响。结论SCFAs是肠腔内碳水化合物细菌群代谢产生的主要阴离子，可保护肠内皮细胞免受氧化损伤，其作用部分是通过细胞特异性HSP25的诱导实现的。
BACKGROUND & AIMS Because short-chain fatty acids (SCFAs) and heat shock proteins (hsps) confer protection to intestinal epithelia cells (IECs), we studied whether SCFAs modulate IEC hsp expression. METHODS Hsp 25, hsp72, and hsc73 protein expression in rat intestinal tissues and IEC-18 cells were determined by Western blot and immunohistochemistry. Cell survival under conditions of oxidant stress (monochloramine) was determined using (51)Cr release in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and increased hsp25, respectively. RESULTS Butyrate induces a time- and concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including the poorly metabolized isobutyate, also induced selective expression of hsp25. Butyrate treatment significantly improved the ability of IEC-18 cells to withstand oxidant (monochloramine) injury. This effect could be blocked in cells in which hsp25 induction by butyrate was blocked by stable hsp25 antisense transfection. Additionally, hsp25-transfected overexpressing IEC-18 cells showed increased resistance to monochloramine. In vivo, increasing dietary fiber increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72 or hsc73 expression. CONCLUSIONS SCFAs, the predominant anions of colonic fluid derived from bacterial flora metabolism of luminal carbohydrates, protect IECs against oxidant injury, an effect mediated in part by cell-specific hsp25 induction.