脱氮酶
氧化应激
谷氨酰胺
细胞生物学
化学
上睑下垂
脂质过氧化
泛素
细胞凋亡
程序性细胞死亡
生物化学
生物
氨基酸
基因
作者
Junfeng Wu,Weitao Han,Yangyang Zhang,Shuangxing Li,Tianyu Qin,Zhengqi Huang,Chao Zhang,Ming Shi,Yu-Liang Wu,Zheng Wang,Bo Gao,Kang Xu,Wei Ye
标识
DOI:10.1089/ars.2023.0384
摘要
Intervertebral disc degeneration (IDD) is closely related to low back pain (LBP), which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, the current study aims to clarify the effect and mechanism of glutamine in IDD.A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine exhibited significant efficacy in mitigating IDD in both ex-vivo and in-vivo experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation in vitro. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting Nrf2 accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation.A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.
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