EFFECT OF ALTERED REDOX STATES ON EXPRESSION AND DNA-FINDING ACTIVITY OF HYPOXIA-INDUCIBLE FACTOR-1
EFFECT OF ALTERED REDOX STATES ON EXPRESSION AND DNA-FINDING ACTIVITY OF HYPOXIA-INDUCIBLE FACTOR-1
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DOI：
10.1006/bbrc.1995.2005
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发表时间：
1995-07-17
影响因子：
3.1
通讯作者：
SEMENZA, GL
中科院分区：
文献类型：
--
作者：
WANG, GL;JIANG, BH;SEMENZA, GL
缺氧诱导因子1（HIF-1）是一种异源二聚体碱性螺旋-环-螺旋（bHLH）-PAS DNA结合蛋白，受细胞氧分压的调节。细胞氧化还原状态与缺氧有关，通过氧化还原调节基因表达的变化和活性氧中间产物的产生。在这里，我们提供的证据表明，细胞氧化还原状态的改变，通过处理细胞与H2 O2或二硫苏糖醇损害缺氧信号传导机制和缺氧细胞中HIF-1 α蛋白的表达。此外，HIF-1的体外DNA结合活性对氧化剂二酰胺和H2 O2以及烷基化剂N-乙基马来酰亚胺敏感。N-乙基马来酰亚胺失活的HIF-1的活性可以通过加入来自非缺氧细胞的核提取物而部分恢复。(C)1995年学术出版社
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix (bHLH)-PAS DNA-binding protein tightly regulated by cellular oxygen tension. Cellular redox states are related to hypoxia by changes in the expression of redox regulated genes and the generation of reactive oxygen intermediates. Here, we provide evidence that alteration of cellular redox states by treating cells with H2O2 or dithiothreitol impairs hypoxia signaling mechanisms and the expression of HIF-1 alpha protein in hypoxic cells. In addition, HIF-1 DNA-binding activity in vitro is sensitive to oxidizing reagents diamide and H2O2 and the alkylating agent N-ethylmaleimide. The activity of N-ethylmaleimide-inactivated HIF-1 can be partially restored by addition of nuclear extract from nonhypoxic cells. (C) 1995 Academic press, Inc.