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

Yan, Yana; Yin, Yandan; Feng, Xiaoran; Yuan, Chen; Shi, Jiamin; Weng, Huachun; Wang, Dan

doi:10.7150/ijms.49246

Cited by 5 publications

(2 citation statements)

References 51 publications

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“…Sii‐Felice K et al discovered that transgenic mice with fanca −/− displayed increased SVZ cell apoptosis, chromosome instability, and increased depletion of NSPC pools, reflecting that FA/BRCA is critical for NSPC survival (Sii‐Felice et al, 2008b). Similar findings were made by Yan et al, where treatment of NE4C cells with homocysteine (Hcy), which can disrupt the FA/Brca1 pathway, was found to exacerbate the DDR induced by MMC in NSCs (Yan et al, 2020). Both studies demonstrate the importance of the Fanconi pathway for NSC in repairing DNA damage and combating ageing.…”

Section: Mechanisms Of Nscs In Response To Dna Damage and Ageingsupporting

confidence: 78%

The role of DNA damage in neural stem cells ageing

Zhong,

Wang,

Yang

et al. 2024

Journal Cellular Physiology

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Neural stem cells (NSCs) are pluripotent stem cells with the potential to differentiate into a variety of nerve cells. NSCs are susceptible to both intracellular and extracellular insults, thus causing DNA damage. Extracellular insults include ultraviolet, ionizing radiation, base analogs, modifiers, alkyl agents and others, while intracellular factors include Reactive oxygen species (ROS) radicals produced by mitochondria, mismatches that occur during DNA replication, deamination of bases, loss of bases, and more. When encountered with DNA damage, cells typically employ three coping strategies: DNA repair, damage tolerance, and apoptosis. NSCs, like many other stem cells, have the ability to divide, differentiate, and repair DNA damage to prevent mutations from being passed down to the next generation. However, when DNA damage accumulates over time, it will lead to a series of alterations in the metabolism of cells, which will cause cellular ageing. The ageing and exhaustion of neural stem cell will have serious effects on the body, such as neurodegenerative diseases. The purpose of this review is to examine the processes by which DNA damage leads to NSCs ageing and the mechanisms of DNA repair in NSCs.

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Section: Mechanisms Of Nscs In Response To Dna Damage and Ageingsupporting

confidence: 78%

The role of DNA damage in neural stem cells ageing

Zhong,

Wang,

Yang

et al. 2024

Journal Cellular Physiology

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“…Growth media formulations are usually serum-free media used for primary NSC cultures obtained from mice or rats, composed of DMEM containing a 2% B27 supplement, 20 ng/mL EGF, 20 ng/mL bFGF, 2 µmol/mL L-glutamine, and 100 U/mL penicillin and streptomycin with or without 4 mg/L folic acid [ 14 , 34 ]. On the other hand, media used for immortalized cell lines usually contain animal sera, and they are formulated as follows: Dulbecco’s modified Eagle’s medium (5 mM glucose) supplemented with 10% fetal bovine serum, 5% horse serum, 2 mM glutamine, 100 U/mL penicillin, and 100 mg/mL streptomycin; or Minimum Essential Medium (MEM; Gibco, Carlsbad, CA, USA) with 10% fetal bovine serum, 2 mM glutamine, 100 U/mL penicillin, and 100 μg/mL streptomycin, for NE4C cells [ 32 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Fetal Bovine Serum or Basic Fibroblast Growth Factor on Cell Survival and the Proliferation of Neural Stem Cells: The Influence of Homocysteine Treatment

Petrović,

Jagečić,

Krasić

et al. 2023

IJMS

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In vitro cell culture is a routinely used method which is also applied for in vitro modeling of various neurological diseases. On the other hand, media used for cell culture are often not strictly standardized between laboratories, which hinders the comparison of the obtained results. Here, we compared the effects of homocysteine (Hcy), a molecule involved in neurodegeneration, on immature cells of the nervous system cultivated in basal medium or media supplemented by either fetal bovine serum or basic fibroblast growth factor. The number of cells in basal media supplemented with basic fibroblast growth factor (bFGF) was 2.5 times higher in comparison to the number of cells in basal media supplemented with fetal bovine serum (FBS). We also found that the neuron-specific β-3-tubulin protein expression dose dependently decreased with increasing Hcy exposure. Interestingly, bFGF exerts a protective effect on β-3-tubulin protein expression at a concentration of 1000 µM Hcy compared to FBS-treated neural stem cells on Day 7. Supplementation with bFGF increased SOX2 protein expression two-fold compared to FBS supplementation. GFAP protein expression increased five-fold on Day 3 in FBS-treated neural stem cells, whereas on Day 7, bFGF increased GFAP expression two-fold compared to FBS-treated neural stem cells. Here, we have clearly shown that the selection of culturing media significantly influences various cellular parameters, which, in turn, can lead to different conclusions in experiments based on in vitro models of pathological conditions.

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Low magnesium in conjunction with high homocysteine increases DNA damage in healthy middle aged Australians

Dhillon,

Deo,

Fenech

2024

Eur J Nutr

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Purpose Magnesium is one of the most common elements in the human body and plays an important role as a cofactor of enzymes required for DNA replication and repair and many other biochemical mechanisms including sensing and regulating one-carbon metabolism deficiencies. Low intake of magnesium can increase the risk of many diseases, in particular, chronic degenerative disorders. However, its role in prevention of DNA damage has not been studied fully in humans so far. Therefore, we tested the hypothesis that magnesium deficiency either on its own or in conjunction with high homocysteine (Hcy) induces DNA damage in vivo in humans. Methods The present study was carried out in 172 healthy middle aged subjects from South Australia. Blood levels of magnesium, Hcy, folate and vitamin B12 were measured. Cytokinesis-Block Micronucleus cytome assay was performed to measure three DNA damage biomarkers: micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) in peripheral blood lymphocytes. Results Data showed that magnesium and Hcy are significantly inversely correlated with each other (r = − 0.299, p < 0.0001). Furthermore, magnesium is positively correlated both with folate (p = 0.002) and vitamin B12 (p = 0.007). Magnesium is also significantly inversely correlated with MN (p < 0.0001) and NPB (p < 0.0001). Individuals with low magnesium and high Hcy exhibited significantly higher frequency of MN and NPBs compared to those with high magnesium and low Hcy (p < 0.0001). Furthermore, there was an interactive effect between these two factors as well in inducing MN (p = 0.01) and NPB (p = 0.048). Conclusions The results obtained in the present study indicate for the first time that low in vivo levels of magnesium either on its own or in the presence of high Hcy increases DNA damage as evident by higher frequencies of MN and NPBs.

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

Cited by 5 publications

References 51 publications

The role of DNA damage in neural stem cells ageing

The role of DNA damage in neural stem cells ageing

Effect of Fetal Bovine Serum or Basic Fibroblast Growth Factor on Cell Survival and the Proliferation of Neural Stem Cells: The Influence of Homocysteine Treatment

Low magnesium in conjunction with high homocysteine increases DNA damage in healthy middle aged Australians

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