Department of Physiology, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Department of Neurosurgery, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea.
Int J Mol Sci. 2023 Jan 9;24(2):1307. doi: 10.3390/ijms24021307.
A spinal cord injury (SCI) is the devastating trauma associated with functional deterioration due to apoptosis. Most laboratory SCI models are generated by a direct impact on an animal's spinal cord; however, our model does not involve the direct impact on the spinal cord. Instead, we use a clamp compression to create an ischemia in the descending aortas of mice. Following the success of inducing an ischemic SCI (ISCI), we hypothesized that this model may show apoptosis via an endoplasmic reticulum (ER) stress pathway. This apoptosis by the ER stress pathway is enhanced by the inducible nitric oxide synthase (iNOS). The ER is used for the protein folding in the cell. When the protein folding capacity is overloaded, the condition is termed the ER stress and is characterized by the accumulation of misfolded proteins inside the ER lumen. The unfolded protein response (UPR) signaling pathways that deal with the ER stress response then become activated. This UPR activates the three signal pathways that are regulated by the inositol-requiring enzyme 1α (IRE1α), the activating transcription factor 6 (ATF6), and the protein kinase RNA-like ER kinase (PERK). IRE1α and PERK are associated with the expression of the apoptotic proteins. Apoptosis caused by an ISCI is assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. An ISCI also reduces synaptophysin and the neuronal nuclear protein (NeuN) in the spinal cord. In conclusion, an ISCI increases the ER stress proteins, resulting in apoptosis in neuronal cells in the spinal cord.
脊髓损伤（SCI）是一种破坏性的创伤，由于细胞凋亡导致功能恶化。大多数实验室 SCI 模型是通过直接作用于动物的脊髓产生的；然而，我们的模型不涉及对脊髓的直接影响。相反，我们使用夹具压迫来创建小鼠降主动脉的缺血。在成功诱导缺血性 SCI（ISCI）后，我们假设该模型可能通过内质网（ER）应激途径引起细胞凋亡。这种通过 ER 应激途径的凋亡被诱导型一氧化氮合酶（iNOS）增强。ER 用于细胞内的蛋白质折叠。当蛋白质折叠能力过载时，这种情况称为 ER 应激，其特征是内质网腔内部错误折叠的蛋白质积累。然后， unfolded protein response (UPR) 信号通路被激活，以应对 ER 应激反应。该 UPR 激活了三个信号通路，分别由肌醇需求酶 1α（IRE1α）、激活转录因子 6（ATF6）和蛋白激酶 RNA 样内质网激酶（PERK）调节。IRE1α 和 PERK 与凋亡蛋白的表达有关。ISCI 引起的细胞凋亡通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）试验进行评估。ISCI 还会减少脊髓中的突触小体和神经元核蛋白（NeuN）。总之，ISCI 增加 ER 应激蛋白，导致脊髓神经元细胞凋亡。
