Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth.
Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth.
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DOI：
10.1152/physiolgenomics.00245.2006
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发表时间：
2007-04
影响因子：
4.6
通讯作者：
E. Bruder;J. J. Lee-J.;E. Widmaier;H. Raff
中科院分区：
文献类型：
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作者：
E. Bruder;J. J. Lee-J.;E. Widmaier;H. Raff
我们推测，肾上腺基因表达的变化介导的增加血浆皮质酮和类固醇生成的大鼠幼崽暴露于缺氧从出生。在当前研究中，大鼠幼仔（及其母体）从出生时就暴露于缺氧环境，并与自由进食或成对进食的含氧量正常母体的幼仔进行比较，以匹配缺氧期间发生的母体摄食量减少。进行微阵列分析，然后用实时PCR进行验证。此外，通过实时PCR分析参与肾上腺功能的选定基因的表达，而不考虑微阵列结果。低氧增加血浆ACTH和皮质酮，而限食没有影响。微阵列显示，许多受缺氧影响的基因编码需要分子氧的蛋白质（单加氧酶，氧化还原酶和电子传递），而只有少数已知参与肾上腺类固醇生成的基因受到影响。有趣的是，参与线粒体功能和中间代谢的基因的表达增加缺氧。实时荧光定量PCR检测到缺氧肾上腺Cyp21a1 mRNA表达的小幅但显著增加。当控制母体食物摄入量减少时，缺氧的影响更加明显，实时PCR检测到星星（244%），Cyp21 a1（208%）和Ldlr（233%）的表达显著增加。目前的研究表明，增加血浆皮质酮在大鼠幼崽是由于缺氧本身，而不是由于减少食物摄入的缺氧大坝。此外，缺氧引起的基因表达的变化，占更多的生产力和有效的类固醇。
We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared with pups from normoxic dams fed ad libitum or pair fed to match the decreased maternal food intake that occurs during hypoxia. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results. Hypoxia increased plasma ACTH and corticosterone, while food restriction had no effect. Microarray revealed that many of the genes affected by hypoxia encode proteins that require molecular oxygen (monooxygenases, oxidoreductases, and electron transport), whereas only a few genes known to be involved in adrenal steroidogenesis were affected. Interestingly, the expression of genes involved in mitochondrial function and intermediary metabolism was increased by hypoxia. Real-time PCR detected a small but significant increase in the expression of Cyp21a1 mRNA in the hypoxic adrenal. When decreased maternal food intake was controlled for, the effects of hypoxia were more pronounced, in that real-time PCR detected significant increases in the expression of Star (244%), Cyp21a1 (208%), and Ldlr (233%). The present study revealed that increased plasma corticosterone in rat pups was due to hypoxia per se, and not as a result of decreased food intake by the hypoxic dam. Furthermore, hypoxia induced changes in gene expression that account for more productive and efficient steroidogenesis.