ReferenceID 2174

Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4

Free Radic Biol Med

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,

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Reference Id
2174
Evidence Id
18764
Core Evidence Id
18764
Source Reference Id
4401
Herb2 Reference Id
HBREF005198
Subject Paper Key
HBIN033053_32896601
Pubmed Id
32896601
Doi
10.1016/j.freeradbiomed.2020.08.029
Paper Title
Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4
Paper Abstract
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.
Journal
Free Radic Biol Med
Publish Year
2020
Experiment Subject
mouse; rat; human
Experiment Type
Animal & Cell Experiment
Phenotype Related
Chondrocyte Dysfunction; Hhcy; Hyperhomocysteinemia; Disorders Of The Vascular, Nervous And Musculoskeletal Systems; Intervertebral Disc Degeneration
Paper Title Cn
Paper Title En
Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via enhancing methylation of GPX4
Bilingual Status
semi_complete