OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling

OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling
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DOI:
10.1016/j.febslet.2010.06.015
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发表时间:
2010-08-04
期刊:
影响因子:
3.5
通讯作者:
Matsushita, Masayuki
Matsushita, Masayuki
中科院分区:
生物学3区
文献类型:
--
作者:
Saito, Ken;Adachi, Noritaka;Matsushita, Masayuki

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2-氧戊二酸和铁依赖性双加氧酶家族对细胞适应氧浓度的变化至关重要。我们发现该家族中OGFOD1基因沉默的细胞在缺血条件下对细胞死亡具有抵抗性,对OGFOD1基因敲除的人细胞进行cDNA芯片分析发现ATPAF1下调。虽然将OGFOD1野生型基因重新引入OGFOD1 KO细胞恢复了ATPAF1 mRNA水平,但催化失活的OGFOD1突变体没有恢复。此外,将ATPAF1基因导入OGFOD1 KO细胞可诱导缺血性细胞死亡。因此,OGFOD1在缺血细胞存活中起重要作用,ATPAF1基因的表达需要OGFOD1铁结合残基。(C) 2010年欧洲生化学会联合会。Elsevier B.V.版权所有。
The 2-oxoglutarate and iron dependent dioxygenase family are crucial for cellular adaptation to changes in oxygen concentration. We found that cells with OGFOD1 gene silencing in this family showed resistance to cell death under ischemia, and cDNA microarray analysis of OGFOD1 knockout human cells revealed downregulation of ATPAF1. Although reintroduction of the OGFOD1 wild-type gene to OGFOD1 KO cells restored ATPAF1 mRNA levels, the catalytically inactive OGFOD1 mutants did not. Furthermore, introduction of ATPAF1 gene to OGFOD1 KO cells induced ischemic cell death. Thus, OGFOD1 plays an important role in ischemic cell survival and an OGFOD1 iron binding residue is required for ATPAF1 gene expression. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.