Department of Neurosurgery, The People's Hospital of Hengshui City, Hengshui, 053000, Hebei, China.
Department of Endocrinology, The People's Hospital of Hengshui City, Hengshui, 053000, Hebei, China.
J Mol Neurosci. 2024 Sep 12;74(3):87. doi: 10.1007/s12031-024-02265-9.
Endoplasmic reticulum stress (ERS) plays an essential role in the development of traumatic brain injury (TBI). We aimed to identify and validate the potential ERS-related genes of TBI through bioinformatics analysis and in vitro cell experiment. A total of 19 TBI and ERS-related genes were obtained from the GeneCards database and Comparative Toxicogenomics Database (CTD). Enrichment analysis primarily enriched in apoptosis. NFE2L2 was identified as a hub gene based on the protein-protein interactions (PPI) network that combined seven ranked methods included in cytoHubba. To further explore the effect of Nrf2, the protein encoded by NFE2L2, on ERS-induced apoptosis, we conducted cell experiments with tert-butylhydroquinone (tBHQ), the classical inducer of Nrf2. Western blot suggested tBHQ pretreatment could diminish ERS and reduce the protein expressions of apoptosis in the primary cultured neuron injury model. These data may establish some theoretical basis for the treatment of TBI and provide inspiration and innovative ideas for clinicians and pathologists to understand TBI comprehensively.
内质网应激(ERS)在创伤性脑损伤(TBI)的发展中起着至关重要的作用。我们旨在通过生物信息学分析和体外细胞实验来鉴定和验证与 TBI 相关的潜在 ERS 相关基因。从基因卡片数据库和比较毒理学基因组数据库(CTD)中总共获得了 19 个与 TBI 和 ERS 相关的基因。富集分析主要富集在细胞凋亡中。基于蛋白互作网络(PPI),结合 cytoHubba 中包含的七种排序方法,确定 NFE2L2 为枢纽基因。为了进一步探讨 Nrf2,即 NFE2L2 编码的蛋白,对 ERS 诱导的细胞凋亡的影响,我们用叔丁基对苯二酚(tBHQ)进行了细胞实验,tBHQ 是 Nrf2 的经典诱导剂。Western blot 表明 tBHQ 预处理可以减轻 ERS 并减少原代培养神经元损伤模型中的细胞凋亡蛋白表达。这些数据可能为 TBI 的治疗建立一些理论基础,并为临床医生和病理学家全面了解 TBI 提供启示和创新思路。