Non-hypoxic induction of HIF-3α by 2-deoxy-D-glucose and insulin
Non-hypoxic induction of HIF-3α by 2-deoxy-D-glucose and insulin
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DOI：
10.1016/j.bbrc.2006.11.027
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发表时间：
2007-01-12
影响因子：
3.1
通讯作者：
Dominiak, Peter
中科院分区：
文献类型：
--
作者：
Heidbreder, Marc;Qadri, Fatimunnisa;Dominiak, Peter
缺氧诱导因子（hif）是细胞适应缺氧的关键介质，但也对非缺氧刺激作出反应。为了阐明与代谢紊乱的关系，hif在胰岛素诱导的低血糖或2-脱氧-d -葡萄糖（2-DG）引起的细胞葡萄糖活化的大鼠中进行了表征。采用实时定量pcr检测HIF-1 α、-2 α、-3 α、-1 β和靶基因glut -1的器官特异性表达。免疫组织化学检测HIF-3 α蛋白的分布。胰岛素和2-DG均导致HIF-3 α mRNA广泛升高。仅在2-DG后，肺和心脏中HIF-2 α mRNA增加，而其他hif未受影响。观察到大脑皮层中HIF-3 α蛋白水平显著升高。HIF诱导的功能意义体现在GLUT-I mRNA表达的增强。HIF-3 α的转录上调代表了体内低血糖和葡萄糖活化的典型反应。这些数据表明HIF系统参与代谢紊乱，例如由糖尿病引起的代谢紊乱。(c) 2006爱思唯尔公司版权所有。
Hypoxia-inducible factors (HIFs) are key mediators of cellular adaptation to hypoxia, but also respond to non-hypoxic stimuli. To clarify involvement in metabolic disturbances, HIFs were characterised in rats subjected to insulin-induced hypoglycaemia or cellular glucoprivation provoked by 2-deoxy-D-glucose (2-DG). Using real-time qPCR, organ-specific expression of HIF-1 alpha, -2 alpha, -3 alpha, -1 beta, and of the target gene GLUT-I was determined. Distribution of HIF-3 alpha proteins was examined by immunohistochemistry. Both, insulin and 2-DG resulted in a widespread increase in HIF-3 alpha mRNA. HIF-2 alpha mRNA increased in lung and heart after 2-DG only, whereas other HIFs remained unaffected. A pronounced increase of protein levels in cerebral cortex was observed for HIF-3 alpha. Functional significance of HIF induction was reflected in enhancement of GLUT-I mRNA. Transcriptional up-regulation of HIF-3 alpha represents a typical response to in vivo hypoglycaemia and glucoprivation. These data suggest an involvement of the HIF system in metabolic derangements as for instance caused by diabetes. (c) 2006 Elsevier Inc. All rights reserved.