Folate affects neural tube development through KDM6A
Objective To investigate the effects of lysine-specific demethylase 6A (KDM6A) on neural tube defects (NTDs) in low folate environment. Methods Mouse embryonic stem cells (SV129), NTD mouse models and NTD human specimens were used. SV129 cells were incubated with 0.02 μmol/L methotrexate (MTX) for 2...
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| Format: | Article |
| Language: | zho |
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Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
2020-02-01
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| Series: | Jichu yixue yu linchuang |
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| Online Access: | http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a190168.pdf |
| _version_ | 1827390522288766976 |
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| author | GAO Jun, LI Jian-ting, XIE Qiu, ZHANG Yong-feng, QIAO Li-na, LIU Chang-yun, WANG Jian-hua |
| author_facet | GAO Jun, LI Jian-ting, XIE Qiu, ZHANG Yong-feng, QIAO Li-na, LIU Chang-yun, WANG Jian-hua |
| author_sort | GAO Jun, LI Jian-ting, XIE Qiu, ZHANG Yong-feng, QIAO Li-na, LIU Chang-yun, WANG Jian-hua |
| collection | DOAJ |
| description | Objective To investigate the effects of lysine-specific demethylase 6A (KDM6A) on neural tube defects (NTDs) in low folate environment. Methods Mouse embryonic stem cells (SV129), NTD mouse models and NTD human specimens were used. SV129 cells were incubated with 0.02 μmol/L methotrexate (MTX) for 24 h, and the folate level was measured by Access 2 Immunoassay system and competitive receptor binding immunoassay. DNA fragmentation and KDM6A expression were detected by Western blot and immunofluorescence. The transcription level of the DNA fragment-related repair gene was measured using the mouse NTD model. The folate content and the expression of KDM6A in human NTD specimens were examined. Results In the low folate environment, the DNA fragmentation increased and the expression of KDM6A protein decreased. At the same time, the expression of DNA fragment repair gene KU80/70 in mouse NTD model decreased (P＜0.05); the expression of low folate NTD specimen KDM6A and KU80 also decreased. Conclusions In a low folate environment, DNA fragmentation increases and KDM6A expression decreased, which may initiate abnormal DNA repair pathways and lead to NTD. |
| first_indexed | 2024-03-08T16:52:55Z |
| format | Article |
| id | doaj.art-598b7c5a03564896b8cd2f9017b89c42 |
| institution | Directory Open Access Journal |
| issn | 1001-6325 |
| language | zho |
| last_indexed | 2024-03-08T16:52:55Z |
| publishDate | 2020-02-01 |
| publisher | Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. |
| record_format | Article |
| series | Jichu yixue yu linchuang |
| spelling | doaj.art-598b7c5a03564896b8cd2f9017b89c422024-01-05T03:14:04ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252020-02-01402161166Folate affects neural tube development through KDM6AGAO Jun, LI Jian-ting, XIE Qiu, ZHANG Yong-feng, QIAO Li-na, LIU Chang-yun, WANG Jian-hua01. School of Clinical Medicine, Weifang Medical University, Weifang 261053;;2. Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001;;3. Central laboratory, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730;;4. Department of Pediatrics, the Affiliated Hospital of Weifang Medical College, Weifang 261053;;5. Biochemical Immunology Laboratory, Capital Institute of Pediatrics, Beijing 100020, ChinaObjective To investigate the effects of lysine-specific demethylase 6A (KDM6A) on neural tube defects (NTDs) in low folate environment. Methods Mouse embryonic stem cells (SV129), NTD mouse models and NTD human specimens were used. SV129 cells were incubated with 0.02 μmol/L methotrexate (MTX) for 24 h, and the folate level was measured by Access 2 Immunoassay system and competitive receptor binding immunoassay. DNA fragmentation and KDM6A expression were detected by Western blot and immunofluorescence. The transcription level of the DNA fragment-related repair gene was measured using the mouse NTD model. The folate content and the expression of KDM6A in human NTD specimens were examined. Results In the low folate environment, the DNA fragmentation increased and the expression of KDM6A protein decreased. At the same time, the expression of DNA fragment repair gene KU80/70 in mouse NTD model decreased (P＜0.05); the expression of low folate NTD specimen KDM6A and KU80 also decreased. Conclusions In a low folate environment, DNA fragmentation increases and KDM6A expression decreased, which may initiate abnormal DNA repair pathways and lead to NTD.http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a190168.pdfneural tube defects|folate|kdm6a|non-homologous end joining |
| spellingShingle | GAO Jun, LI Jian-ting, XIE Qiu, ZHANG Yong-feng, QIAO Li-na, LIU Chang-yun, WANG Jian-hua Folate affects neural tube development through KDM6A Jichu yixue yu linchuang neural tube defects|folate|kdm6a|non-homologous end joining |
| title | Folate affects neural tube development through KDM6A |
| title_full | Folate affects neural tube development through KDM6A |
| title_fullStr | Folate affects neural tube development through KDM6A |
| title_full_unstemmed | Folate affects neural tube development through KDM6A |
| title_short | Folate affects neural tube development through KDM6A |
| title_sort | folate affects neural tube development through kdm6a |
| topic | neural tube defects|folate|kdm6a|non-homologous end joining |
| url | http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a190168.pdf |
| work_keys_str_mv | AT gaojunlijiantingxieqiuzhangyongfengqiaolinaliuchangyunwangjianhua folateaffectsneuraltubedevelopmentthroughkdm6a |