Alleviating Oxidative Damage-Induced Telomere Attrition: a Potential Mechanism for Inhibition by Folic Acid of Apoptosis in Neural Stem Cells.
Mol Neurobiol
; 59(1): 590-602, 2022 Jan.
Article
en En
| MEDLINE
| ID: mdl-34741234
ABSTRACT
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 µM) and then incubated for 24 h with a combination of folic acid and an oxidant (100-µM 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Telómero
/
Apoptosis
/
Estrés Oxidativo
/
Células-Madre Neurales
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Ácido Fólico
/
Antioxidantes
Límite:
Animals
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China