Differential expression of adenine nucleotide converting enzymes in mitochondrial intermembrane space: a potential role of adenylate kinase isozyme 2 in neutrophil differentiation.
Differential expression of adenine nucleotide converting enzymes in mitochondrial intermembrane space: a potential role of adenylate kinase isozyme 2 in neutrophil differentiation.
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DOI：
10.1371/journal.pone.0089916
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Noma T
中科院分区：
文献类型：
--
作者：
Tanimura A;Horiguchi T;Miyoshi K;Hagita H;Noma T
线粒体膜间隙（IMS）中的腺嘌呤核苷酸动力学在氧化磷酸化中起关键作用。在先前的研究中，果蝇腺苷酸激酶同工酶2（Dak 2）敲除的果蝇在幼虫阶段的发育致死的报道。此外，另外两项研究报告说，AK 2是网状细胞发育不全（RD）的一个负责基因，RD是一种以严重联合免疫缺陷和耳聋为特征的人类疾病。因此，线粒体AK 2可能在造血分化和个体发育中起重要作用。在IMS中发现了另外三种腺嘌呤核苷酸代谢酶，包括线粒体肌酸激酶（CKMT 1和CKMT 2）和核苷二磷酸激酶亚型D（NDPK-D）。虽然这些激酶产生ADP的ATP合成，其参与RD仍不清楚，仍然是一个悬而未决的问题。在这项研究中，这些线粒体激酶的mRNA和蛋白质的表达，首先在小鼠ES细胞，8天的胚胎，和7周龄的成年小鼠。结果发现，它们的表达是时空调节的，并且Ak 2仅在骨髓中表达，骨髓是成人的主要造血组织。在随后的实验中，我们确定了在巨噬细胞分化过程中AK 2和CKMT 1的表达增加，以及使用HL-60细胞作为造血分化的体外模型在中性粒细胞分化过程中AK 2的排他性产生。此外，AK 2敲低特异性抑制中性粒细胞分化而不影响巨噬细胞分化。这些数据表明，AK 2是必不可少的中性粒细胞分化，并表明一个可能的因果关系AK 2缺乏症和中性粒细胞减少症的RD。
Adenine nucleotide dynamics in the mitochondrial intermembrane space (IMS) play a key role in oxidative phosphorylation. In a previous study, Drosophila adenylate kinase isozyme 2 (Dak2) knockout was reported to cause developmental lethality at the larval stage in Drosophila melanogaster. In addition, two other studies reported that AK2 is a responsible gene for reticular dysgenesis (RD), a human disease that is characterized by severe combined immunodeficiency and deafness. Therefore, mitochondrial AK2 may play an important role in hematopoietic differentiation and ontogenesis. Three additional adenine nucleotide metabolizing enzymes, including mitochondrial creatine kinases (CKMT1 and CKMT2) and nucleoside diphosphate kinase isoform D (NDPK-D), have been found in IMS. Although these kinases generate ADP for ATP synthesis, their involvement in RD remains unclear and still an open question. In this study, mRNA and protein expressions of these mitochondrial kinases were firstly examined in mouse ES cells, day 8 embryos, and 7-week-old adult mice. It was found that their expressions are spatiotemporally regulated, and Ak2 is exclusively expressed in bone marrow, which is a major hematopoietic tissue in adults. In subsequent experiments, we identified increased expression of both AK2 and CKMT1 during macrophage differentiation and exclusive production of AK2 during neutrophil differentiation using HL-60 cells as an in vitro model of hematopoietic differentiation. Furthermore, AK2 knockdown specifically inhibited neutrophil differentiation without affecting macrophage differentiation. These data suggest that AK2 is indispensable for neutrophil differentiation and indicate a possible causative link between AK2 deficiency and neutropenia in RD.
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影响因子：
3.5
作者：
Köhler, C;Gahm, A;Zhivotovsky, B
通讯作者：
Zhivotovsky, B
DOI：
10.1111/j.1432-1033.1988.tb14469.x
发表时间：
1988-12-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BANDLOW, W;STROBEL, G;MAGDOLEN, V
通讯作者：
MAGDOLEN, V
影响因子：
4.8
作者：
Burkart, Alison;Shi, Xiarong;Corvera, Silvia
通讯作者：
Corvera, Silvia
DOI：
10.1016/j.cbpb.2009.01.006
发表时间：
2009-05-01
影响因子：
2.2
作者：
Fujisawa, Koichi;Murakami, Ryutaro;Noma, Takafumi
通讯作者：
Noma, Takafumi
DOI：
10.1073/pnas.77.5.2936
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BREITMAN, TR;SELONICK, SE;COLLINS, SJ
通讯作者：
COLLINS, SJ