HIF-1α Mediates TRAIL-Induced Neuronal Apoptosis via Regulating DcR1 Expression Following Traumatic Brain Injury

• Published in: Frontiers in cellular neuroscience 2020-08, Vol.14, p.192-192
• Main Authors: Fang, Yuanjian, Lu, Jianan, Wang, Xiaoyu, Wu, Haijian, Mei, Shuhao, Zheng, Jingwei, Xu, Shenbin, Lenahan, Cameron, Chen, Sheng, Zhang, Jianmin, Hong, Yuan
• Format: Article
• Language: English
• Subjects: Apoptosis; Cellular Neuroscience; Death; death receptor 5; decoy receptor; Edema; Hypoxia; hypoxia-induced factor-1α; Hypoxia-inducible factor 1a; Immunofluorescence; Ischemia; Laboratory animals; Ligands; Localization; Microglia; Neurological diseases; Peptides; Proteins; Signal transduction; siRNA; Studies; TRAIL protein; Trauma; Traumatic brain injury; Tumor cells; tumor necrosis factor-related apoptosis-inducing ligand; Tumor necrosis factor-TNF; Western blotting
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2020.00192

Abstract Background: Neuronal apoptosis involved in secondary injury following traumatic brain injury (TBI) significantly contributes to the poor outcomes of patients with TBI. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can selectively induce apoptosis of tumor cells. Hypoxia factor (HIF) -1α is a controversial factor that mediates the neuronal apoptotic pathway. Herein, we hypothesize that HIF-1α may mediate the TRAIL-induced neuronal apoptosis after TBI. Methods: We used western blots and immunofluorescence to study the expression and cell localization of the TRAIL and death receptor 5 (DR5) after TBI in rats. Soluble DR5 (sDR5) administration was used to block the TRAIL-induced neuronal death and neural deficits. HIF-1α inhibitor 2ME and agonist DMOG were used to study the role of HIF-1α on the TRAIL-induced neuronal death. Meanwhile, HIF-1α siRNA was used to investigate the role of HIF-1α on the TRAIL-induced neuronal death in vitro. Results: The expression of microglia located TRAIL and neuron located DR5 were significantly upregulated after TBI. sDR5 significantly attenuated TRAIL-induced neuronal apoptosis and neurological deficits. 2ME decreased neuronal apoptosis, lesion area, brain edema, and improve neurological function via increased expression of TRAIL decoy receptor 1 (DcR1), which inhibited TRAIL-induced apoptosis after TBI. Administration of DMOG produced the opposite effect of 2ME. Similarly, HIF-1α siRNA attenuated TRAIL-induced neuronal death via increased DcR1 expression in vitro. Conclusion: Our findings suggested that TRAIL/DR5 signaling pathway plays an important role after neuronal apoptosis after TBI. HIF-1α mediates TRAIL-induced neuronal apoptosis by regulating DcR1 expression following TBI.