Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4
Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4
复制标题
同型半胱氨酸通过增强 GPX4 甲基化诱导氧化应激和髓核铁死亡
DOI：
10.1016/j.freeradbiomed.2020.08.029
复制
发表时间：
2020-11-20
影响因子：
7.4
通讯作者：
Zhao, Fengdong
中科院分区：
文献类型：
--
作者：
Zhang, Xuyang;Huang, Zhaobo;Zhao, Fengdong
同型半胱氨酸（Hcy）是一种参与基因甲基化的氨基酸。病理状态高同型半胱氨酸血症（HHcy）时，Hcy的血浆浓度升高，这增加了血管、神经和肌肉骨骼系统疾病的风险，包括软骨细胞功能障碍。本研究旨在利用一系列技术探讨Hcy在椎间盘退变（IVDD）中的作用。临床流行病学研究表明，HHcy是人类IVDD的独立危险因素。用大鼠髓核细胞进行细胞培养表明，Hcy促进了一种退行性细胞表型（包括氧化应激增加和铁凋亡引起的细胞死亡），这是由上调GPX4甲基化介导的。IVDD的小鼠体内“穿刺”模型显示，叶酸（用于治疗人类HHcy）降低了饮食诱导的HHcy促进IVDD的能力。我们得出结论，Hcy通过增强GPX4甲基化来上调髓核氧化应激和铁凋亡，是IVDD的一个新的促进因素。
Homocysteine (Hcy) is an amino acid involved in gene methylation. Plasma concentration of Hcy is elevated in the pathological condition hyperhomocysteinemia (HHcy), which increases the risk of disorders of the vascular, nervous and musculoskeletal systems, including chondrocyte dysfunction. The present study aimed to explore the role of Hcy in intervertebral disc degeneration (IVDD), using a range of techniques. A clinical epidemiological study showed that HHcy is an independent risk factor for human IVDD. Cell culture using rat nucleus pulposus cells showed that Hcy promotes a degenerative cell phenotype (involving increased oxidative stress and cell death by ferroptosis) which is mediated by upregulated methylation of GPX4. An in-vivo mouse 'puncture' model of IVDD showed that folic acid (which is used to treat HHcy in humans) reduced the ability of diet-induced HHcy to promote IVDD. We conclude that Hcy upregulates oxidative stress and ferroptosis in the nucleus pulposus via enhancing GPX4 methylation, and is a new contributing factor in IVDD.