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Homocysteine inhibits neural stem cells survival by inducing DNA interstrand cross-links via oxidative stress.
Neurosci Lett. 2016 Dec 02; 635:24-32.NL

Abstract

Elevated plasma levels of homocysteine have been implicated in neurodevelopmental and neurodegenerative disorders in human studies. Although the molecular mechanisms underlying the effects of homocysteine (Hcy) cytotoxicity on the nervous system are not yet fully unknown, induction of DNA interstrand cross-links and inhibition of neural stem cells (NSCs) survival may be involved. The objective of our study was to investigate the effects of Hcy on DNA interstrand cross-links in NSCs, and to explore its possible mechanisms. We also found that Hcy induced cell DNA damage on a dose-dependent manner and evoked reactive oxidative species (ROS) production, leading to elevated apoptosis in NSCs. Moreover, Hcy exposure activated the Fanconi anemia (FA) pathway, which was characterized by increases in monoubiquitination of Fanci and Fancd2 and enhancement of the interaction between above two proteins. On contrary, N-Acety-l-Cysteine (NAC) decreased Hcy-evoked ROS production and significantly ameliorated DNA damage and improved cell survival. These data suggest that Hcy may play a role in the pathogenesis of neurological diseases via a molecular mechanism that induces DNA interstrand cross-links via oxidative stress and involves in negative regulation of NSCs survival.

Authors+Show Affiliations

Department of Neonatology, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.Department of Surgery, Wenzhou Medical University Second Affiliated Hospital, Wenzhou, Zhejiang, China.Department of Neonatology, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.Department of Neonatology, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.Department of Neonatology, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China. Electronic address: 13111240011@fudan.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27773793

Citation

Wang, Dan, et al. "Homocysteine Inhibits Neural Stem Cells Survival By Inducing DNA Interstrand Cross-links Via Oxidative Stress." Neuroscience Letters, vol. 635, 2016, pp. 24-32.
Wang D, Chen YM, Ruan MH, et al. Homocysteine inhibits neural stem cells survival by inducing DNA interstrand cross-links via oxidative stress. Neurosci Lett. 2016;635:24-32.
Wang, D., Chen, Y. M., Ruan, M. H., Zhou, A. H., Qian, Y., & Chen, C. (2016). Homocysteine inhibits neural stem cells survival by inducing DNA interstrand cross-links via oxidative stress. Neuroscience Letters, 635, 24-32. https://doi.org/10.1016/j.neulet.2016.10.032
Wang D, et al. Homocysteine Inhibits Neural Stem Cells Survival By Inducing DNA Interstrand Cross-links Via Oxidative Stress. Neurosci Lett. 2016 Dec 2;635:24-32. PubMed PMID: 27773793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine inhibits neural stem cells survival by inducing DNA interstrand cross-links via oxidative stress. AU - Wang,Dan, AU - Chen,Yi-Ming, AU - Ruan,Miao-Hua, AU - Zhou,Ai-Hua, AU - Qian,Yan, AU - Chen,Chao, Y1 - 2016/10/20/ PY - 2016/09/04/received PY - 2016/10/13/revised PY - 2016/10/19/accepted PY - 2016/10/30/pubmed PY - 2017/8/16/medline PY - 2016/10/30/entrez KW - DNA damage KW - Fanconi anemia pathway KW - Homocysteine KW - Interstrand cross-link KW - Neural stem cell KW - Oxidative stress SP - 24 EP - 32 JF - Neuroscience letters JO - Neurosci. Lett. VL - 635 N2 - Elevated plasma levels of homocysteine have been implicated in neurodevelopmental and neurodegenerative disorders in human studies. Although the molecular mechanisms underlying the effects of homocysteine (Hcy) cytotoxicity on the nervous system are not yet fully unknown, induction of DNA interstrand cross-links and inhibition of neural stem cells (NSCs) survival may be involved. The objective of our study was to investigate the effects of Hcy on DNA interstrand cross-links in NSCs, and to explore its possible mechanisms. We also found that Hcy induced cell DNA damage on a dose-dependent manner and evoked reactive oxidative species (ROS) production, leading to elevated apoptosis in NSCs. Moreover, Hcy exposure activated the Fanconi anemia (FA) pathway, which was characterized by increases in monoubiquitination of Fanci and Fancd2 and enhancement of the interaction between above two proteins. On contrary, N-Acety-l-Cysteine (NAC) decreased Hcy-evoked ROS production and significantly ameliorated DNA damage and improved cell survival. These data suggest that Hcy may play a role in the pathogenesis of neurological diseases via a molecular mechanism that induces DNA interstrand cross-links via oxidative stress and involves in negative regulation of NSCs survival. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/27773793/Homocysteine_inhibits_neural_stem_cells_survival_by_inducing_DNA_interstrand_cross_links_via_oxidative_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(16)30784-4 DB - PRIME DP - Unbound Medicine ER -