<br>硒代蛋氨酸通过调节IP3R/GRP75/VDAC1复合物恢复线粒体动态平衡，减少脂多糖诱导的神经元凋亡,Journal of Cellular Physiology

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硒代蛋氨酸通过调节IP3R/GRP75/VDAC1复合物恢复线粒体动态平衡，减少脂多糖诱导的神经元凋亡
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2024-01-14 , DOI: 10.1002/jcp.31190
Anqi Xu ₁ , Yixuan Wang ₁ , Dongliu Luo ₁ , Yu Xia ₁ , Hua Xue ₂ , Haidong Yao ₃ , Shu Li ₁

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硒（Se）作为人体必需的微量元素之一，在体内起到抗炎、抗氧化、增强免疫等作用。此外，硒还可以改善各种因素引起的神经系统损伤。早期研究已经描述了线粒体动态失衡在脂多糖（LPS）诱导的神经损伤中的重要作用。肌醇1,4,5-三磷酸受体（IP3R）/葡萄糖调节蛋白75（GRP75）/电压依赖性阴离子通道1（VDAC1）复合物被认为是调节线粒体动力学的关键。然而，尚不清楚硒代蛋氨酸 (SeMet) 是否对 IP3R/GRP75/VDAC1 复合物有任何影响。因此，本研究的目的是确定SeMet是否可以减轻LPS引起的脑损伤，并阐明IP3R/GRP75/VDAC1复合物在其中的功能。我们使用蛋鸡和原代鸡神经细胞在体内和体外建立了 SeMet 和/或 LPS 暴露模型。我们注意到 SeMet 逆转了内质网应激（ERS）和线粒体动力学的不平衡，并显着阻止了神经元凋亡的发生。我们通过对蛋鸡脑组织的形态学观察以及ERS、IP3R/GRP75/VDAC1复合物、钙信号(Ca ²⁺ )、线粒体动力学和细胞凋亡等相关基因的检测得出了这一发现。除此之外，我们还发现当SeMet作为神经保护剂发挥作用时，IP3R/GRP75/VDAC1复合物对于控制内质网和线粒体之间的Ca ²⁺转运至关重要。总之，我们的研究结果首次揭示了 SeMet 减轻 LPS 诱导的神经元凋亡的具体机制。因此，SeMet 在治疗和预防神经系统疾病（如神经退行性疾病）方面具有巨大潜力。

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By regulating the IP3R/GRP75/VDAC1 complex to restore mitochondrial dynamic balance, selenomethionine reduces lipopolysaccharide-induced neuronal apoptosis

Selenium (Se), as one of the essential trace elements, plays an anti-inflammatory, antioxidation, and immune-enhancing effect in the body. In addition, Se can also improve nervous system damage induced by various factors. Earlier studies have described the important role of mitochondrial dynamic imbalance in lipopolysaccharide (LPS)-induced nerve injury. The inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (GRP75)/voltage-dependent anion channel 1 (VDAC1) complex is considered to be the key to regulating mitochondrial dynamics. However, it is not clear whether Selenomethionine (SeMet) has any influence on the IP3R/GRP75/VDAC1 complex. Therefore, the aim of this investigation was to determine whether SeMet can alleviate LPS-induced brain damage and to elucidate the function of the IP3R/GRP75/VDAC1 complex in it. We established SeMet and/or LPS exposure models in vivo and in vitro using laying hens and primary chicken nerve cells. We noticed that SeMet reversed endoplasmic reticulum stress (ERS) and the imbalance in mitochondrial dynamics and significantly prevented the occurrence of neuronal apoptosis. We made this finding by morphological observation of the brain tissue of laying hens and the detection of related genes such as ERS, the IP3R/GRP75/VDAC1 complex, calcium signal (Ca²⁺), mitochondrial dynamics, and apoptosis. Other than that, we also discovered that the IP3R/GRP75/VDAC1 complex was crucial in controlling Ca²⁺ transport between the endoplasmic reticulum and the mitochondrion when SeMet functions as a neuroprotective agent. In summary, our results revealed the specific mechanism by which SeMet alleviated LPS-induced neuronal apoptosis for the first time. As a consequence, SeMet has great potential in the treatment and prevention of neurological illnesses (like neurodegenerative diseases).

更新日期：2024-01-14

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