Metabolic changes in the one-carbon metabolism-related amino acids during etoposide-induced cellular senescence of neuronal cells.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology Pub Date : 2025-08-01 Epub Date: 2025-06-30 DOI:10.1007/s10616-025-00803-w

Wang Jiahao, Jun Kameyama, Miyako Udono, Yoshinori Katakura

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引用次数: 0

Abstract

A large-scale longitudinal epidemiological study by the Hisayama study revealed that the concentration of one-carbon metabolism-related amino acids in the serum changes with age and that there is a link between these fluctuations and the risk of developing dementia (Hata et al. in Am J Epidemiol 188:1637-1645, 2019; Mihara et al. in Sci Rep 12:12427, 2022). Therefore, the aim of this study was to focus on age-related changes in one-carbon metabolism-related amino acids and elucidate the regulatory basis of these changes. Treatment with etoposide, an anti-cancer drug, induced cellular senescence in SH-SY5Y cells, as indicated by increased senescence-associated β galactosidase activity and upregulated expression of senescence markers p16 and p21. Liquid chromatography-mass spectrometry analysis revealed that the intracellular amino acid concentrations, particularly those involved in the one-carbon metabolism, were elevated in senescent cells, including those of methionine, S-adenosylmethionine, S-adenosylhomocysteine (SAH), homocysteine (Hcys), and related metabolites. The results of the expression analysis focused on the enzyme genes involved in Hcys metabolism and revealed that the induction of cellular senescence upregulated adenosylhomocysteinase like 1/2 (AHCYL1/L2), which convert SAH to Hcys. Additionally, the genes involved in Hcys metabolism via the sulphuration pathway (KYAT1/3 and CTH) were significantly upregulated. Because Hcys has been implicated in aging, further investigations focused on AHCYL1/L2. Gene knockdown of AHCYL1/L2 in etoposide-treated cells reduced p16 and p21 expression, indicating that AHCYL1/L2 is essential for cellular senescence induction. These findings suggest that Hcys accumulation and its metabolic enzymes play a crucial role in cellular senescence.

Supplementary information: The online version contains supplementary material available at 10.1007/s10616-025-00803-w.

查看原文本刊更多论文

依托泊苷诱导的神经元细胞衰老过程中单碳代谢相关氨基酸的代谢变化。

Hisayama研究的一项大规模纵向流行病学研究显示，血清中一碳代谢相关氨基酸的浓度随着年龄的增长而变化，这些波动与患痴呆症的风险之间存在联系(Hata et al. in Am J epidemiology, 88:1637-1645, 2019；Mihara et al.科学进展（英文版），2012)。因此，本研究的目的是关注与年龄相关的单碳代谢相关氨基酸的变化，并阐明这些变化的调控基础。用抗癌药物依托泊苷治疗SH-SY5Y细胞可诱导细胞衰老，衰老相关β半乳糖苷酶活性增加，衰老标志物p16和p21表达上调。液相色谱-质谱分析显示，衰老细胞内氨基酸浓度，特别是与单碳代谢有关的氨基酸浓度，包括蛋氨酸、s -腺苷蛋氨酸、s -腺苷同型半胱氨酸（SAH）、同型半胱氨酸（Hcys）及其相关代谢物的浓度升高。对参与Hcys代谢的酶基因进行了表达分析，发现细胞衰老的诱导上调了将SAH转化为Hcys的腺苷型同型半胱氨酸酶1/2 （AHCYL1/L2）。此外，通过硫酸途径参与Hcys代谢的基因（KYAT1/3和CTH）显著上调。由于Hcys与衰老有关，进一步的研究集中在AHCYL1/L2上。在etoposid处理的细胞中，AHCYL1/L2基因敲低可降低p16和p21的表达，表明AHCYL1/L2对细胞衰老的诱导至关重要。这些发现表明Hcys的积累及其代谢酶在细胞衰老中起着至关重要的作用。补充信息：在线版本包含补充资料，可在10.1007/s10616-025-00803-w获得。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.