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Identification by differential display of the IF1 inhibitor peptide of ATP synthase/ATPase as a gene inducible in rat liver by pregnenolone 16 alpha-carbonitrile

机译:通过差异显示IF合酶抑制剂ATP合酶/ ATPase肽的鉴定作为孕烯醇酮16α-腈在大鼠肝脏中诱导的基因

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The synthetic steroid, pregnenolone-16 alpha -carbonitrile (PCN), activates hepatic metabolism and elimination of xenobiotics mediated by its interaction with the PXR, a nuclear receptor that binds PCN and such glucocorticoids as dexamethasone (Dex). We used mRNA differential display to define further the domain of genes under the control of PCN/PXR. We found 76 cDNA fragments representing mRNAs differentially expressed in the Liver of rats treated with PCN or Dex. Sequence analysis of one of these revealed a PCN induced cDNA fragment as IF1, an inhibitor peptide of ATP synthase/ATPase complex. Northern blot analysis revealed that IF1 was detectable in untreated liver and was induced 2-3 fold following treatment with PCN. IF1 mRNA was not detected in lung, heart, kidney, or testes of control or PCN treated rats. We conclude that IF1 inhibitor peptide is a novel representative of an apparently large set of previously unrecognized genes coordinately controlled by the PCN/PXR system to maintain homeostasis during toxic stress. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 32]
机译:合成类固醇pregnenolone-16α-腈(PCN)激活肝脏代谢,并消除其与PXR相互作用介导的异源生物,PXR是与PCN和地塞米松(Dex)等糖皮质激素结合的核受体。我们使用mRNA差异显示来进一步定义PCN / PXR控制下的基因域。我们发现76个cDNA片段代表在用PCN或Dex治疗的大鼠肝脏中差异表达的mRNA。其中之一的序列分析显示,PCN诱导的cDNA片段为IF1,它是ATP合酶/ ATPase复合物的抑制剂肽。 Northern印迹分析显示,在未经治疗的肝脏中可检测到IF1,并在用PCN治疗后被诱导2-3倍。在对照或PCN处理的大鼠的肺,心脏,肾脏或睾丸中未检测到IF1 mRNA。我们得出的结论是,IF1抑制剂肽是由PCN / PXR系统协调控制以在毒性胁迫期间维持体内平衡的明显大批先前无法识别的基因的新颖代表。 (C)2000 Elsevier Science Inc.保留所有权利。 [参考:32]

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