• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

小鼠线粒体ND4、CYTB和COX3基因的多态性影响衰老过程中的造血作用。

Polymorphisms of the murine mitochondrial ND4, CYTB and COX3 genes impact hematopoiesis during aging.

作者信息

Kretzschmar Christin, Roolf Catrin, Timmer Katrin, Sekora Anett, Knübel Gudrun, Murua Escobar Hugo, Fuellen Georg, Ibrahim Saleh M, Tiedge Markus, Baltrusch Simone, Jaster Robert, Köhling Rüdiger, Junghanss Christian

机构信息

Department of Medicine III - Hematology/Oncology/Palliative Care, Rostock University Medical Center, Rostock, Germany.

Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock, Germany.

出版信息

Oncotarget. 2016 Nov 15;7(46):74460-74472. doi: 10.18632/oncotarget.11952.

DOI:10.18632/oncotarget.11952
PMID:27626489
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5342679/
Abstract

During aging, mitochondrial DNA (mtDNA) can accumulate mutations leading to increasing levels of reactive oxygen species (ROS). Increased ROS were described to activate formerly quiescent hematopoietic stem cells (HSC). Mutations in mtDNA were shown to enhance the risk for myelodysplastic syndrome and leukemia. However, the complex relationship between mtDNA variations, ROS and aging of the hematopoietic system is not fully understood.Herein, three mouse strains with mtDNA polymorphisms in genes of respiratory chain complexes I (ND4), III (CYTB) and IV (COX3) were compared to a reference strain during aging. Analysis focused on ROS and ATP levels, bone marrow composition and blood counts. Additionally, hematopoietic restoration capacity following cytotoxic stress was tested.Mice with polymorphisms in ND4 and CYTB gene had significantly decreasing ROS levels in bone marrow cells during aging, without effecting ATP levels. In addition, the frequency of stem and progenitor cells increased during aging but the amount of lymphocytes in the peripheral blood decreased during aging.In summary, the presence of mtDNA polymorphisms affecting the respiratory chain complexes I, III and IV was associated with altered ROS levels as well as changes in BM and peripheral blood composition during aging.

摘要

在衰老过程中，线粒体DNA（mtDNA）会积累突变，导致活性氧（ROS）水平升高。研究表明，ROS增加会激活先前静止的造血干细胞（HSC）。mtDNA突变会增加骨髓增生异常综合征和白血病的风险。然而，mtDNA变异、ROS与造血系统衰老之间的复杂关系尚未完全明确。在此，将呼吸链复合物I（ND4）、III（CYTB）和IV（COX3）基因存在mtDNA多态性的三种小鼠品系与一种对照品系在衰老过程中进行比较。分析重点在于ROS和ATP水平、骨髓组成及血细胞计数。此外，还测试了细胞毒性应激后的造血恢复能力。ND4和CYTB基因存在多态性的小鼠在衰老过程中骨髓细胞中的ROS水平显著降低，而ATP水平不受影响。此外，衰老过程中干细胞和祖细胞的频率增加，但外周血中的淋巴细胞数量减少。总之，影响呼吸链复合物I、III和IV的mtDNA多态性的存在与衰老过程中ROS水平的改变以及骨髓和外周血组成的变化有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/ed9936659c8c/oncotarget-07-74460-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/a6785fcc0018/oncotarget-07-74460-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/19d2d061cffe/oncotarget-07-74460-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/e830eeaaaee5/oncotarget-07-74460-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/f457f65846bd/oncotarget-07-74460-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/ed9936659c8c/oncotarget-07-74460-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/a6785fcc0018/oncotarget-07-74460-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/19d2d061cffe/oncotarget-07-74460-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/e830eeaaaee5/oncotarget-07-74460-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/f457f65846bd/oncotarget-07-74460-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b67/5342679/ed9936659c8c/oncotarget-07-74460-g005.jpg

相似文献

1
Polymorphisms of the murine mitochondrial ND4, CYTB and COX3 genes impact hematopoiesis during aging.小鼠线粒体ND4、CYTB和COX3基因的多态性影响衰老过程中的造血作用。
Oncotarget. 2016 Nov 15;7(46):74460-74472. doi: 10.18632/oncotarget.11952.
2
Polymorphism in Murine mtATP8 Gene Correlates with Decreased Reactive Oxygen Species in Aging Hematopoietic Cells.小鼠线粒体ATP8基因多态性与衰老造血细胞中活性氧减少相关。
In Vivo. 2016 Nov 12;30(6):751-760. doi: 10.21873/invivo.10991.
3
Uncoupling protein 2 deficiency results in higher neutrophil counts and lower B-cell counts during aging in mice.解偶联蛋白2缺乏导致小鼠衰老过程中嗜中性粒细胞计数升高和B细胞计数降低。
Exp Hematol. 2016 Nov;44(11):1085-1091.e2. doi: 10.1016/j.exphem.2016.08.003. Epub 2016 Aug 17.
4
Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production.体细胞线粒体DNA突变会导致衰老表型，而不影响活性氧的产生。
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17993-8. doi: 10.1073/pnas.0508886102. Epub 2005 Dec 6.
5
Respiratory function decline and DNA mutation in mitochondria, oxidative stress and altered gene expression during aging.衰老过程中的呼吸功能衰退、线粒体DNA突变、氧化应激及基因表达改变。
Chang Gung Med J. 2009 Mar-Apr;32(2):113-32.
6
Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus.线粒体DNA完整性降低、含量减少及转录水平升高与圆锥角膜相关。
PLoS One. 2016 Oct 26;11(10):e0165580. doi: 10.1371/journal.pone.0165580. eCollection 2016.
7
Mitochondrial Electron Transport Chain Complex II Dysfunction Causes Premature Aging of Hematopoietic Stem Cells.线粒体电子传递链复合物II功能障碍导致造血干细胞过早衰老。
Stem Cells. 2023 Jan 30;41(1):39-49. doi: 10.1093/stmcls/sxac072.
8
Time-course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging.小鼠大脑中线粒体基因表达的时间进程：对衰老过程中线粒体功能障碍、氧化损伤及细胞色素c的影响
J Neurochem. 2005 Feb;92(3):494-504. doi: 10.1111/j.1471-4159.2004.02884.x.
9
Transcriptome sequencing reveals the involvement of reactive oxygen species in the hematopoiesis from Chinese mitten crab Eriocheir sinensis.转录组测序揭示活性氧参与中华绒螯蟹的造血过程。
Dev Comp Immunol. 2018 May;82:94-103. doi: 10.1016/j.dci.2017.12.030. Epub 2018 Jan 5.
10
Age-dependent accumulation of mtDNA mutations in murine hematopoietic stem cells is modulated by the nuclear genetic background.小鼠造血干细胞中线粒体DNA（mtDNA）突变的年龄依赖性积累受核基因背景调控。
Hum Mol Genet. 2007 Feb 1;16(3):286-94. doi: 10.1093/hmg/ddl457. Epub 2006 Dec 21.

引用本文的文献

1
Phylogenetic Reassessment of Murinae Inferred from the Mitogenome of the Monotypic Genus Endemic to Southeast Asia: New Insights into Genetic Diversity Erosion.基于东南亚特有单型属线粒体基因组对鼠亚科系统发育的重新评估：对遗传多样性侵蚀的新见解
Biology (Basel). 2025 Jul 28;14(8):948. doi: 10.3390/biology14080948.
2
Heteroplasmy and Individual Mitogene Pools: Characteristics and Potential Roles in Ecological Studies.异质性与个体线粒体基因库：生态研究中的特征及潜在作用
Biology (Basel). 2023 Nov 20;12(11):1452. doi: 10.3390/biology12111452.
3
The Interplay between Dysregulated Metabolism and Epigenetics in Cancer.

本文引用的文献

1
Reduced adolescent-age spatial learning ability associated with elevated juvenile-age superoxide levels in complex I mouse mutants.在复合体I小鼠突变体中，青少年期空间学习能力降低与幼年超氧化物水平升高有关。
PLoS One. 2015 Apr 8;10(4):e0123863. doi: 10.1371/journal.pone.0123863. eCollection 2015.
2
A mutation in the NADH-dehydrogenase subunit 2 suppresses fibroblast aging.烟酰胺腺嘌呤二核苷酸（NADH）脱氢酶亚基2中的一种突变可抑制成纤维细胞衰老。
Oncotarget. 2015 Apr 20;6(11):8552-66. doi: 10.18632/oncotarget.3298.
3
Hematopoietic stem cell aging.
代谢失调与癌症表观遗传学的相互作用
Biomolecules. 2023 Jun 5;13(6):944. doi: 10.3390/biom13060944.
4
Mitochondrial Contributions to Hematopoietic Stem Cell Aging.线粒体对造血干细胞衰老的贡献。
Int J Mol Sci. 2021 Oct 15;22(20):11117. doi: 10.3390/ijms222011117.
5
Identification of key genes and pathways associated with feed efficiency of native chickens based on transcriptome data via bioinformatics analysis.基于转录组数据的生物信息学分析鉴定与地方鸡饲料效率相关的关键基因和通路。
BMC Genomics. 2020 Apr 9;21(1):292. doi: 10.1186/s12864-020-6713-y.
6
Mitochondrial Genome (mtDNA) Mutations that Generate Reactive Oxygen Species.产生活性氧的线粒体基因组（mtDNA）突变
Antioxidants (Basel). 2019 Sep 11;8(9):392. doi: 10.3390/antiox8090392.
7
Decitabine demonstrates antileukemic activity in B cell precursor acute lymphoblastic leukemia with MLL rearrangements.地西他滨在伴有 MLL 重排的 B 细胞前体急性淋巴细胞白血病中表现出抗白血病活性。
J Hematol Oncol. 2018 May 4;11(1):62. doi: 10.1186/s13045-018-0607-3.
造血干细胞衰老。
Curr Opin Immunol. 2014 Aug;29:86-92. doi: 10.1016/j.coi.2014.05.002. Epub 2014 Jun 3.
4
Inbred mouse strains reveal biomarkers that are pro-longevity, antilongevity or role switching.近交系小鼠品系揭示了具有延长寿命、缩短寿命或角色转换作用的生物标志物。
Aging Cell. 2014 Aug;13(4):729-38. doi: 10.1111/acel.12226. Epub 2014 May 23.
5
Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome.氧化应激导致骨髓增生异常综合征小鼠模型中突变频率增加。
Leuk Res. 2014 Jan;38(1):95-102. doi: 10.1016/j.leukres.2013.07.008. Epub 2013 Aug 16.
6
Mitochondrial DNA mutations in human tumor cells.人类肿瘤细胞中的线粒体DNA突变。
Oncol Lett. 2012 Nov;4(5):868-872. doi: 10.3892/ol.2012.874. Epub 2012 Aug 23.
7
Mitochondrial genome instability and ROS enhance intestinal tumorigenesis in APC(Min/+) mice.线粒体基因组不稳定性和 ROS 增强 APC(Min/+) 小鼠的肠道肿瘤发生。
Am J Pathol. 2012 Jan;180(1):24-31. doi: 10.1016/j.ajpath.2011.10.003. Epub 2011 Nov 3.
8
Signal transduction by reactive oxygen species.活性氧物种的信号转导。
J Cell Biol. 2011 Jul 11;194(1):7-15. doi: 10.1083/jcb.201102095.
9
Highly reactive oxygen species: detection, formation, and possible functions.高反应性氧物种：检测、形成和可能的功能。
Cell Mol Life Sci. 2011 Jun;68(12):2067-79. doi: 10.1007/s00018-011-0682-x. Epub 2011 May 2.
10
Molecular targets of oxidative stress.氧化应激的分子靶点。
Biochem J. 2011 Mar 1;434(2):201-10. doi: 10.1042/BJ20101695.