Alleviating Oxidative Damage-Induced Telomere Attrition: a Potential Mechanism for Inhibition by Folic Acid of Apoptosis in Neural Stem Cells

被引:9
作者
Li, Zhenshu [1 ]
Li, Wen [1 ,2 ,3 ]
Zhou, Dezheng [1 ]
Zhao, Jing [1 ]
Ma, Yue [1 ]
Huang, Ling [1 ]
Dong, Cuixia [1 ]
Wilson, John X. [4 ]
Huang, Guowei [1 ,2 ,3 ,5 ]
机构
[1] Tianjin Med Univ, Sch Publ Hlth, Dept Nutr & Food Sci, 22 Qixiangtai Rd, Tianjin 300070, Peoples R China
[2] Tianjin Key Lab Environm Nutr & Publ Hlth, Tianjin 300070, Peoples R China
[3] Ctr Int Collaborat Res Environm Nutr & Publ Hlth, Tianjin 300070, Peoples R China
[4] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Exercise & Nutr Sci, Buffalo, NY 14214 USA
[5] Tianjin Med Univ, Prov & Minist Cosponsored Collaborat Innovat Ctr, Tianjin 300070, Peoples R China
基金
中国国家自然科学基金;
关键词
Folic acid; Apoptosis; Telomere attrition; Oxidative damage; Neural stem cell; In vitro; STRESS; PROLIFERATION; DNA; LENGTH; DIFFERENTIATION; ACCUMULATION;
D O I
10.1007/s12035-021-02623-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
DNA oxidative damage can cause telomere attrition or dysfunction that triggers cell senescence and apoptosis. The hypothesis of this study is that folic acid decreases apoptosis in neural stem cells (NSCs) by preventing oxidative stress-induced telomere attrition. Primary cultures of NSCs were incubated for 9 days with various concentrations of folic acid (0-40 mu M) and then incubated for 24 h with a combination of folic acid and an oxidant (100-mu M hydrogen peroxide, H2O2), antioxidant (10-mM N-acetyl-L-cysteine, NAC), or vehicle. Intracellular folate concentration, apoptosis rate, cell proliferative capacity, telomere length, telomeric DNA oxidative damage, telomerase activity, intracellular reactive oxygen species (ROS) levels, cellular oxidative damage, and intracellular antioxidant enzyme activities were determined. The results showed that folic acid deficiency in NSCs decreased intracellular folate concentration, cell proliferation, telomere length, and telomerase activity but increased apoptosis, telomeric DNA oxidative damage, and intracellular ROS levels. In contrast, folic acid supplementation dose-dependently increased intracellular folate concentration, cell proliferative capacity, telomere length, and telomerase activity but decreased apoptosis, telomeric DNA oxidative damage, and intracellular ROS levels. Exposure to H2O2 aggravated telomere attrition and oxidative damage, whereas NAC alleviated the latter. High doses of folic acid prevented telomere attrition and telomeric DNA oxidative damage by H2O2. In conclusion, inhibition of telomeric DNA oxidative damage and telomere attrition in NSCs may be potential mechanisms of inhibiting NSC apoptosis by folic acid.
引用
收藏
页码:590 / 602
页数:13
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