High homocysteine promotes telomere dysfunction and chromosomal instability in human neuroblastoma SH-SY5Y cells
High homocysteine promotes telomere dysfunction and chromosomal instability in human neuroblastoma SH-SY5Y cells
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高同型半胱氨酸促进人神经母细胞瘤SH-SY5Y细胞端粒功能障碍和染色体不稳定
DOI：
10.1016/j.mrgentox.2020.503197
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Wang Xu
中科院分区：
文献类型：
--
作者：
Hu Xialian;Guo Xihan;Ni Juan;Wang Han;Cao Neng;Liang Ziqing;Wang Xu
端粒是线性染色体末端的特殊结构，它保护染色体末端免受降解、重组和错误修复。极短的端粒长度(TL)可能导致染色体不稳定(CIN)，导致肿瘤促进，在较高水平上，细胞死亡和肿瘤抑制。同型半胱氨酸(Hcy)是一种参与一碳代谢的含硫氨基酸。血浆同型半胱氨酸升高是致癌的危险因素。人SH-SY5Y神经母细胞瘤细胞用病理生理浓度的同型半胱氨酸(15-120μM)处理14天和28天。采用胞质分裂阻断微核细胞组法测定细胞停滞(核分裂指数，NDI)、细胞死亡(细胞凋亡和坏死)和CIN(双核细胞微核、核质桥和核芽)。用定量聚合酶链式反应检测TL及端粒酶催化亚单位基因hTERT的表达。结果表明，同型半胱氨酸诱导TL和fl延长，并引起端粒酶逆转录酶基因表达的改变。TL伸长与增加有关，CIN、Hcy降低NDI，增加细胞死亡。本研究表明，在肿瘤细胞中存在Hcy和TL之间的串扰，并支持高Hcy通过TL的异常延长和CIN的升高抑制细胞分裂和促进肿瘤细胞死亡的观点。
Telomeres, specialized structures at the ends of linear chromosomes, protect chromosome ends from degrada-.tion, recombination, and mis-repair. Critically short telomere length (TL) may result in chromosome instability.(CIN), causing tumor promotion and, at higher levels, cell death and tumor suppression. Homocysteine (Hcy) is a.sulfur-containing amino acid involved in one-carbon metabolism. Elevated plasma Hcy is a cancer risk factor..Human SH-SY5Y neuroblastoma cells were treated with pathophysiological concentrations of Hcy (15–120 μM).for 14 and 28 days. The cytokinesis-block micronucleus cytome assay was used to determine cytostasis (nuclear.division index, NDI), cell death (apoptosis and necrosis), and CIN (micronuclei, nucleoplasmic bridges, and.nuclear buds in binucleated cells). Quantitative PCR was used to measure TL and the expression of hTERT, the.gene encoding the catalytic subunit of telomerase for TL elongation. The results showed that Hcy induced.elongation of TL and fluctuating changes in expression of hTERT. TL elongation was associated with increased.CIN. Hcy decreased the NDI and increased cell death. This study shows that there is cross-talk between Hcy and.TL in tumor cells and supports the concept that high Hcy inhibits cell division and promotes the death of tumor.cells by abnormal elongation of TL and elevation of CIN.