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脊髓再生模型中的细胞因子信号转导抑制蛋白 1 。

Suppressors of cytokine signaling 1 protein in a regenerative model of the spinal cord.

机构信息

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, 226019 Nantong, Jiangsu, China.

出版信息

J Integr Neurosci. 2021 Sep 30;20(3):585-594. doi: 10.31083/j.jin2003062.

Abstract

Demyelination is one of the pathological outcomes that occur immediately following spinal cord injury. Protection of oligodendrocytes against death/apoptosis proves to be beneficial for the preservation of neurological functions. Suppressors of cytokine signaling 1 protein inhibit the harmful effects of several inflammatory cytokines on oligodendrocytes, but its roles in spinal cord injury (SCI) induced apoptosis of oligodendrocytes remain unclear. We cloned suppressors of cytokine signaling 1 cDNA from (Japanese gecko) and analyzed the protein structure revealing the conserved domains contained in other vertebrate suppressors of cytokine signaling 1 proteins. The gecko suppressors of cytokine signaling 1 protein expression were increased in the injured spinal cord following gecko tail amputation and displayed colocalization with oligodendrocytes. The enforced expression of gecko suppressors of cytokine signaling 1 by adenovirus in the Gsn3 gecko oligodendrocyte cell line demonstrated that gecko suppressors of cytokine signaling 1 significantly suppressed cell apoptosis-induced by glucose deprivation. Determination of apoptosis-related proteins revealed that gecko suppressors of cytokine signaling 1 was able to activate extracellular regulated protein kinases (ERK) and serine/threonine protein kinases (Akt). The results presented a distinct protective role of gecko suppressors of cytokine signaling 1 in the regenerative model of the spinal cord, which may provide new cues for central nervous system repair in mammals.

摘要

脱髓鞘是脊髓损伤后立即发生的一种病理结果。保护少突胶质细胞不发生死亡/凋亡被证明对维持神经功能有益。细胞因子信号转导抑制因子 1 蛋白抑制几种炎症细胞因子对少突胶质细胞的有害影响,但它在脊髓损伤(SCI)诱导的少突胶质细胞凋亡中的作用尚不清楚。我们从(日本壁虎)克隆了细胞因子信号转导抑制因子 1 cDNA,并分析了蛋白质结构,揭示了其他脊椎动物细胞因子信号转导抑制因子 1 蛋白中包含的保守结构域。在壁虎尾巴截断后,受伤的脊髓中细胞因子信号转导抑制因子 1 的表达增加,并与少突胶质细胞共定位。通过腺病毒在 Gsn3 壁虎少突胶质细胞系中强制表达壁虎细胞因子信号转导抑制因子 1 表明,壁虎细胞因子信号转导抑制因子 1 显著抑制了葡萄糖剥夺诱导的细胞凋亡。凋亡相关蛋白的测定表明,壁虎细胞因子信号转导抑制因子 1 能够激活细胞外调节蛋白激酶(ERK)和丝氨酸/苏氨酸蛋白激酶(Akt)。结果表明,壁虎细胞因子信号转导抑制因子 1 在脊髓再生模型中具有明显的保护作用,这可能为哺乳动物中枢神经系统修复提供新的线索。

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