Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet
Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet
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DOI：
10.1093/carcin/bgn144
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发表时间：
2008-07-01
期刊：
影响因子：
4.7
通讯作者：
Lupton, Joanne R.
中科院分区：
文献类型：
--
作者：
Crim, Kristy Covert;Sanders, Lisa M.;Lupton, Joanne R.
本研究的总体目标是将丁酸盐的作用从其纤维来源中分离出来，并在体内确定它是否上调结肠组蛋白乙酰化、p21（Waf 1/Cip 1）表达（p21）和细胞凋亡，以及这种事件的后遗症是否对异常隐窝病灶（ACF）形成具有保护作用。为80只Sprague-Dawley大鼠提供规定的饲料，其中玉米油或鱼油作为脂质来源，含有靶向在结肠中释放的+/-丁酸酯的胶囊和+/-氧化偶氮甲烷（AOM）（每组10只大鼠）。饮食提供了11周，并在终止结肠细胞核组蛋白H4和p21的表达，通过免疫组化，细胞凋亡的末端脱氧核苷酸转移酶生物素-dUTP缺口末端标记法测定和异常的隐窝数和多样性进行了计数。还定量管腔丁酸水平。AOM注射抑制p21的表达，这是由丁酸补充逆转。虽然丁酸增强p21的表达与两种膳食脂肪来源，p21的增加导致细胞凋亡的增加和减少ACF与鱼油，但没有影响细胞凋亡和增加ACF与玉米油。脂肪、丁酸盐（纤维）和p21表达之间的这种显著相互作用，其中一种组合是保护性的，另一种是促进结肠癌发生的，这加强了将饮食视为化学预防中关键因素的重要性。
The overall goal of this research was to separate out the effects of butyrate from its fiber source and determine in vivo if it upregulates colonic histone acetylation, p21(Waf1/Cip1) expression (p21) and apoptosis and if this sequela of events is protective against aberrant crypt foci (ACF) formation. Eighty Sprague-Dawley rats were provided defined diets with either corn oil or fish oil as the lipid source, +/- butyrate-containing capsules targeted for release in the colon and +/- azoxymethane (AOM) (10 rats per group). Diets were provided for 11 weeks and at termination colonocyte nuclear histone H4 and p21 expression were determined by immunohistochemistry, apoptosis was measured by the terminal deoxynucleotide transferase biotin-dUTP nick end labeling assay and aberrant crypt numbers and multiplicity were enumerated. Luminal butyrate levels were also quantified. AOM injection repressed p21 expression, which was reversed by butyrate supplementation. Although butyrate enhanced p21 expression with both dietary lipid sources, the increase in p21 resulted in an increase in apoptosis and decrease in ACF with fish oil, but had no effect on apoptosis and increased ACF with corn oil. This significant interaction between fat, butyrate (fiber) and p21 expression with one combination being protective and the other promotive of colon carcinogenesis reinforces the importance of considering diet as a key factor in chemoprevention.