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ID 117929
Author
Tanimura, Ayako Prefectural University of Kumamoto KAKEN Search Researchers
Hagita, Hiroko Tokushima University
Minami, Hisanori Kobe Gakuin University
Keywords
adenylate kinase 2
mitochondria
neutrophil differentiation
reticular dysgenesis
CRISPR/Cas9
fructose
Content Type
Journal Article
Description
Mitochondrial ATP production plays an important role in most cellular activities, including growth and differentiation. Previously we reported that Adenylate kinase 2 (AK2) is the main ADP supplier in the mitochondrial intermembrane space in hematopoietic cells, especially in the bone marrow. AK2 is crucial for the production of neutrophils and T cells, and its deficiency causes reticular dysgenesis. However, the relationship between ADP supply by AK2 and neutrophil differentiation remains unclear. In this study, we used CRISPR/Cas9 technology to establish two heterozygous AK2 knock-out HL-60 clones as models for reticular dysgenesis. Their AK2 activities were about half that in the wild-type (WT). Furthermore, neutrophil differentiation was impaired in one of the clones. In silico analysis predicted that the obtained mutations might cause a structural change in AK2. Time course microarray analysis of the WT and mutants revealed that similar gene clusters responded to all-trans retinoic acid treatment, but their expression was lower in the mutants than in WT. Application of fructose partially restored neutrophil differentiation in the heterozygous knock-out HL-60 clone after all-trans retinoic acid treatment. Collectively, our study suggests that the mutation of N-terminal region in AK2 might play a role in AK2-dependent neutrophil differentiation and fructose could be used to treat AK2 deficiency.
Journal Title
International Journal of Molecular Sciences
ISSN
14220067
Publisher
MDPI
Volume
23
Issue
24
Start Page
16089
Published Date
2022-12-17
Rights
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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language
eng
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departments
Oral Sciences