硫化氢亚慢性治疗对tbi诱导的铁下垂和Wnt信号通路介导的认知缺陷的神经保护作用

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Cellular and Molecular Neurobiology Pub Date : 2023-11-01 Epub Date: 2023-08-25 DOI:10.1007/s10571-023-01399-5
Jie Chen, Zhennan Chen, Dongyu Yu, Yufei Yan, Xiuli Hao, Mingxia Zhang, Tong Zhu
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引用次数: 0

摘要

新的证据表明,靶向铁下垂可能是治疗创伤性脑损伤(TBI)的潜在治疗策略。硫化氢(H2S)已被证明在TBI中发挥神经保护作用,但对H2S在TBI诱导的铁下垂中的作用知之甚少。此外,有报道称Wnt信号通路也能积极调节铁下垂。然而,H2S是否通过Wnt信号通路抑制TBI后铁下垂仍不清楚。在本研究中,我们首先发现H2S除了减轻神经元损伤和认知障碍外,还能显著减轻异常铁积累,降低脂质过氧化,提高谷胱甘肽过氧化物酶4的表达,证明H2S在TBI后具有强大的抗铁下沉作用。此外,Wnt3a或利普司他汀-1治疗获得了类似的结果,这表明激活Wnt信号通路可以使细胞对tbi后铁死亡的易感程度降低。更重要的是,Wnt信号通路抑制剂XAV939几乎逆转了H2S处理引起的铁亡失活和神经元损失减少,证实了Wnt信号通路参与H2S的抗铁亡作用。综上所述,Wnt信号通路可能是H2S抗TBI铁沉作用的关键机制。创伤性脑损伤后慢性期出现铁超载、抗氧化系统受损和脂质过氧化等与铁中毒相关的变化。然而,NaHS亚慢性治疗降低了对tbi诱导的铁下垂的易感性,至少部分是通过激活Wnt信号通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Neuroprotective Effect of Hydrogen Sulfide Subchronic Treatment Against TBI-Induced Ferroptosis and Cognitive Deficits Mediated Through Wnt Signaling Pathway.

Neuroprotective Effect of Hydrogen Sulfide Subchronic Treatment Against TBI-Induced Ferroptosis and Cognitive Deficits Mediated Through Wnt Signaling Pathway.

Emerging evidence shows that targeting ferroptosis may be a potential therapeutic strategy for treating traumatic brain injury (TBI). Hydrogen sulfide (H2S) has been proven to play a neuroprotective role in TBI, but little is known about the effects of H2S on TBI-induced ferroptosis. In addition, it is reported that the Wnt signaling pathway can also actively regulate ferroptosis. However, whether H2S inhibits ferroptosis via the Wnt signaling pathway after TBI remains unclear. In this study, we first found that in addition to alleviating neuronal damage and cognitive impairments, H2S remarkably attenuated abnormal iron accumulation, decreased lipid peroxidation, and improved the expression of glutathione peroxidase 4, demonstrating the potent anti-ferroptosis action of H2S after TBI. Moreover, Wnt3a or liproxstatin-1 treatment obtained similar results, suggesting that activation of the Wnt signaling pathway can render the cells less susceptible to ferroptosis post-TBI. More importantly, XAV939, an inhibitor of the Wnt signaling pathway, almost inversed ferroptosis inactivation and reduction of neuronal loss caused by H2S treatment, substantiating the involvement of the Wnt signaling pathway in anti-ferroptosis effects of H2S. In conclusion, the Wnt signaling pathway might be the critical mechanism in realizing the anti-ferroptosis effects of H2S against TBI. TBI induces ferroptosis-related changes characterized by iron overload, impaired antioxidant system, and lipid peroxidation at the chronic phase after TBI. However, NaHS subchronic treatment reduces the susceptibility to TBI-induced ferroptosis, at least partly by activating the Wnt signaling pathway.

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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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