Role of diacylglycerol induced by hypoxia in the regulation of HIF-1α activity
Role of diacylglycerol induced by hypoxia in the regulation of HIF-1α activity
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缺氧诱导的二酰甘油在调节HIF-1α活性中的作用
DOI：
10.1016/j.bbrc.2004.01.015
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发表时间：
2004
影响因子：
3.1
通讯作者：
M. Landázuri
中科院分区：
文献类型：
--
作者：
Elisa Temes;Silvia Martin;Julián Aragonés;David R. Jones;G. Olmos;I. Mérida;M. Landázuri
缺氧诱导因子1(HIF-1)是适应低氧环境的关键转录因子。我们以前报道过低氧通过二甘油酸激酶(DGK)的活性诱导磷脂酸(PA)的积累，并提供了这种PA的产生调节HIF-1表达的证据。在这里，我们报告低氧还会在不同类型的细胞中产生显着的二酰甘油(DAG)积累。先前提出的磷脂酰胆碱磷脂酶C(PC-PLC)/鞘磷脂合成酶(SMS)活性的抑制剂D609，特异性地阻断了低氧依赖的DAG积聚和低氧诱导的HIF-1表达。我们发现DAG依赖的蛋白激酶C(PKC)亚型在HIF-1的表达调控中不起重要作用。D609抑制低氧诱导的PA积累，提示在此条件下DAG可作为DGK转化为PA的底物。因此，这项工作为参与HIF-1表达调控的DAG/PA依赖的细胞内机制的存在提供了新的证据。
Hypoxia-inducible factor 1 (HIF-1) is a critical transcription factor for the adaptation to lowered oxygen environments. We have previously reported that hypoxia induced phosphatidic acid (PA) accumulation through diacylglycerol kinase (DGK) activity and provided evidence that this PA production regulated HIF-1 expression. Here we report that hypoxia also produces a marked intracellular accumulation of diacylglycerol (DAG) in different cell types. The previously proposed inhibitor of phosphatidylcholine phospholipase C (PC-PLC)/sphingomyelin synthase (SMS) activities, D609, specifically abrogates both hypoxia-dependent DAG accumulation and hypoxia-induced HIF-1 expression. We show that DAG-dependent protein kinase C (PKC) isoforms do not play an essential role in the regulation of HIF-1 expression. D609 inhibits PA accumulation triggered by hypoxia, suggesting that DAG could act as substrate for its conversion into PA by DGK upon these conditions. Therefore, this work provides novel evidence for the existence of DAG/PA-dependent intracellular mechanisms involved in the regulation of HIF-1 expression.
影响因子：
15.9
作者：
Goldberg, M;Zhang, HL;Steinberg, SF
通讯作者：
Steinberg, SF