Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells

doi:10.7150/ijms.49246

科研成果详情

题名	Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells
作者	Yan, Yana 1; Yin, Yandan 2; Feng, Xiaofang1; Chen, Yuan 1; Shi, Jiamin1; Weng, Huachun1; Wang, Dan 1
发表日期	2020
发表期刊	INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	homocysteine DNA damage Fanconi anemia pathway Brca1 neural stem cell
其他关键词	FANCONI-ANEMIA ; REPAIR PATHWAY ; DEFICIENCY ; PROTEIN ; FANCD2 ; BRCA1 ; FANCI-FANCD2 ; NEURONS ; CANCER
摘要	There is existing evidence that elevated homocysteine (Hcy) levels are risk factors for some neurodegenerative disorders. The pathogenesis of neurological diseases could be contributed to excessive cell dysfunction and death caused by defective DNA damage response (DDR) and accumulated DNA damage. Hcy is a neurotoxic amino acid and acts as a DNA damage inducer. However, it is not clear whether Hcy participates in the DDR. To investigate the effects of Hcy on DNA damage and the DDR, we employed mitomycin C (MMC) to cause DNA damage in NE4C murine neural stem cells (NSCs). Compared to treatment with MMC alone, we found that co-treatment with MMC and Hcy worsened DNA damage and increased death in NE4C cells. Intriguingly, in this DNA damage model mimicked by MMC, immunoblotting results showed that the monoubiquitination levels of Fanconi anemia complementation group I (Fanci) and Fanconi anemia complementation group D2 (Fancd2) were decreased to about 60.3% and 55.7% by supplementing cell culture medium with Hcy, indicating Hcy inactivates the function of Fanci and Fancd2 in DNA damage conditions. Given Breast Cancer 1 (BRCA1) is an important downstream of FANCD2, we next detected the interaction between Fancd2 and Brca1 in NE4C cells. Compared to treatment with MMC alone, the Fancd2-Brca1 interaction and the amount of Brca1 on chromatin were decreased when cells were co-exposed to MMC and Hcy, suggesting Hcy could impair the Fanconi anemia (FA)/Brca1 pathway. Taken together, our study demonstrates that Hcy may enhance cell death, which contributes to the accumulation of DNA damage and promotion of hypersensitivity to cytotoxicity by impairing the FA/Brca1 pathway in murine NSCs in the presence of DNA damage.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81701485]
出版者	IVYSPRING INT PUBL
出版地	LAKE HAVEN
ISSN	1449-1907
卷号	17 期号:16 页码:2477-2486
DOI	10.7150/ijms.49246
页数	10
WOS类目	Medicine, General & Internal
WOS研究方向	General & Internal Medicine
WOS记录号	WOS:000573072200001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33029090
PMC记录号	PMC7532487
SCOPUSEID	2-s2.0-85091315615
通讯作者地址	[Weng, Huachun]Department of Pediatrics,The First Affiliated Hospital of Wenzhou Medical University,No. 2 Fuxue Road,Wenzhou,325000,China ; [Wang, Dan]Department of Pediatrics,The First Affiliated Hospital of Wenzhou Medical University,No. 2 Fuxue Road,Wenzhou,325000,China
Scopus学科分类	Medicine (all)
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/13134
专题	附属第一医院第二临床医学院、附属第二医院、育英儿童医院_儿科学
通讯作者	Weng, Huachun; Wang, Dan
作者单位	1.Department of Pediatrics,The First Affiliated Hospital of Wenzhou Medical University,No. 2 Fuxue Road,Wenzhou,325000,China; 2.Department of Pediatrics,Taizhou Women and Children’s Hospital of Wenzhou Medical University,Taizhou,318000,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Yan, Yana,Yin, Yandan,Feng, Xiaofang,et al. Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells[J]. INTERNATIONAL JOURNAL OF MEDICAL SCIENCES,2020,17(16):2477-2486.
APA	Yan, Yana., Yin, Yandan., Feng, Xiaofang., Chen, Yuan., Shi, Jiamin., ... & Wang, Dan. (2020). Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells. INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 17(16), 2477-2486.
MLA	Yan, Yana,et al."Homocysteine aggravates DNA damage by impairing the FA/Brca1 Pathway in NE4C murine neural stem cells".INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 17.16(2020):2477-2486.