Restraint stress alters the duodenal expression of genes important for lipid metabolism in rat
Restraint stress alters the duodenal expression of genes important for lipid metabolism in rat
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DOI：
10.1016/j.tox.2006.08.009
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发表时间：
2006-10-29
期刊：
影响因子：
4.5
通讯作者：
Takeda, Eiji
中科院分区：
文献类型：
--
作者：
Sato, Tadatoshi;Yamamoto, Hironori;Takeda, Eiji
应激，如创伤和损伤，已知会引起各种组织中的转录变化;然而，关于组织特异性基因表达响应应激的信息很少。在这里，我们已经研究了十二指肠基因表达的大鼠进行全身制动，以阐明的应激反应的机制，在胃的组织之一，是最敏感的外部压力。DNA微阵列分析显示，制动2周引起了大鼠十二指肠基因表达的巨大变化：165个基因表达水平变化超过2倍（103个上调; 62个下调）。此外，这些基因的功能分类表明，固定优先刺激与脂质代谢相关的基因的表达，包括基因编码的n-线粒体HMG-CoA合成酶，在生酮的关键酶;溶质载体27 A2，脂肪酸转运蛋白;和二烯酰CoA还原酶，在P-氧化的关键酶。为了阐明介导这些固定诱导的变化的因素，我们用地塞米松和过氧化氢处理大鼠和小肠IEC-6细胞。在大鼠和IEC-6细胞中，地塞米松治疗诱导的基因表达的变化，模仿固定介导的线粒体HMG-CoA合酶和二烯酰CoA还原酶转录本的表达增加，表明应激诱导的糖皮质激素合成介导，至少部分，在十二指肠的应激反应。这些结果表明，固定可能会改变脂质代谢在小肠通过修改特定基因的表达，小肠可能会寻求保护自己免受应激诱导的损伤。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Stress, such as trauma and injury, is known to cause transcriptional changes in various tissues; however, there is little information on tissue-specific gene expression in response to stress. Here, we have examined duodenal gene expression in rats subjected to whole-body immobilization in order to elucidate the mechanism underlying the stress response in the duodenum-one of the tissues that is most sensitive to external stress. DNA microarray analysis revealed that the immobilization for 2 weeks caused great changes in gene expression in the rat duodenum: 165 genes exhibited more than a two-fold change in expression level (103 up-regulated; 62 down-regulated). In addition, functional classification of these genes showed that immobilization preferentially stimulated the expression of genes related to lipid metabolism, including genes encoding n-mitochondrial HMG-CoA synthase, a key enzyme in ketogenesis; solute carrier 27A2, a fatty acid transporter; and dienoyl CoA reductase, a key enzyme in P-oxidation. To elucidate the factors mediating these immobilization-induced changes, we treated rats and small intestinal IEC-6 cells with dexamethasone and hydrogen peroxide. In both rats and IEC-6 cells, treatment with dexamethasone induced changes in gene expression that mimicked the immobilization-mediated increase in expression of the mitochondrial HMG-CoA synthase and dienoyl CoA reductase transcripts, suggesting that stress-induced synthesis of glucocorticoid hormones mediates, at least in part, the stress response in the duodenum. These results suggest that immobilization may alter lipid metabolism in the small intestine by modifying the expression of specific genes through which the small intestine may seek to protect itself from stress-induced damage. (c) 2006 Elsevier Ireland Ltd. All rights reserved.