Identification and Validation of Endoplasmic Reticulum Stress-Related Gene in Traumatic Brain Injury

IF 2.8 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Molecular Neuroscience Pub Date : 2024-09-12 DOI:10.1007/s12031-024-02265-9

Gengshui Zhao, Yongqi Fu, Chao Yang, Xuehui Yang, Xiaoxiao Hu

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Abstract

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.

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创伤性脑损伤中内质网应激相关基因的鉴定与验证

内质网应激（ERS）在创伤性脑损伤（TBI）的发展过程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，鉴定和验证潜在的 TBI ERS 相关基因。我们从基因卡片数据库（GeneCards database）和比较毒物基因组学数据库（CTD）中共获得了 19 个 TBI 和 ERS 相关基因。富集分析主要富集在细胞凋亡中。根据蛋白质-蛋白质相互作用（PPI）网络，结合 cytoHubba 中的七种排序方法，NFE2L2 被确定为一个枢纽基因。为了进一步探讨NFE2L2编码的蛋白Nrf2对ERS诱导的细胞凋亡的影响，我们用Nrf2的经典诱导剂叔丁基对苯二酚（tBHQ）进行了细胞实验。Western 印迹表明，在原代培养的神经元损伤模型中，叔丁基对苯二酚预处理可减轻 ERS 并降低凋亡蛋白的表达。这些数据可为创伤性脑损伤的治疗提供一些理论依据，并为临床医生和病理学家全面了解创伤性脑损伤提供启发和创新思路。

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来源期刊

Journal of Molecular Neuroscience 医学-神经科学

CiteScore

6.60

自引率

3.20%

发文量

142

审稿时长

1 months

期刊介绍： The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.