叶酸对体外人成纤维细胞和黑色素瘤细胞端粒长度和染色体稳定性的影响:叶酸和5-甲基四氢叶酸的比较。

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY
Mutagenesis Pub Date : 2023-06-20 DOI:10.1093/mutage/gead007
Han Wang, Juan Ni, Xihan Guo, Jinglun Xue, Xu Wang
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引用次数: 1

摘要

端粒长度(TL)由人类端粒酶逆转录酶(hTERT)维持;端粒酶和/或TRF1/TRF2(庇护蛋白的核心成分)通过不同的机制,对染色体稳定性和细胞存活至关重要。叶酸包括一组必需的维生素B9,参与DNA合成和甲基化。本研究旨在探讨叶酸(FA)和5-甲基四氢叶酸(5-MeTHF)对端粒酶阴性BJ和端粒酶阳性A375细胞TL、染色体稳定性和细胞存活的影响。BJ和A375细胞在添加FA或5-MeTHF(22.6或2260 nM)的改性培养基中培养28 d。RT-qPCR检测TL和mRNA表达。采用CBMN-Cyt法检测染色体不稳定性(CIN)和细胞死亡情况。结果表明,FA和5-MeTHF缺失的BJ细胞TL伸长异常。A375细胞的TL在fa -缺陷条件下无明显变化,而在5- methf -缺陷条件下明显拉长。在BJ和A375细胞中,FA和5-MeTHF缺乏导致TRF1、TRF2和hTERT表达降低,CIN升高和细胞死亡;高浓度5-MeTHF诱导TL延长,CIN升高,TRF1和TRF2表达升高,hTERT表达降低。这些结果表明,叶酸缺乏导致端粒酶阴性和阳性细胞的TL不稳定,与5-MeTHF相比,FA在维持TL和染色体稳定方面更有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate.

Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA and 5-MeTHF deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.

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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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