Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury.
Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury.
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丝氨酸 - 硫代蛋白激酶激活可能是减少脊髓损伤后神经元凋亡的有效靶标。
DOI：
10.4103/1673-5374.170313
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发表时间：
2015-11
影响因子：
6.1
通讯作者：
Liu SY
中科院分区：
文献类型：
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作者：
Jin M;Yang YW;Cheng WP;Lu JK;Hou SY;Dong XH;Liu SY
缺血诱导的神经细胞凋亡的信号机制知之甚少。我们研究了缺血性脊髓损伤后凋亡相关信号转导通路的影响，包括细胞外信号调节激酶（ERK）、丝氨酸-苏氨酸蛋白激酶（Akt）和c-Jun N-末端激酶（JNK）信号通路。我们通过在左锁骨下动脉插入导管球囊25分钟建立了大鼠急性脊髓损伤模型。大鼠模型表现出明显的后肢功能障碍。脊髓前角和中央管有大量凋亡细胞。凋亡神经元数量在伤后48小时最多。磷酸化Akt（p-Akt）和磷酸化ERK（p-ERK）的表达在再灌注后立即增加，在4 h（p-Akt）或2 h（p-ERK）达到高峰，12 h下降，24 h又增加。再灌注后磷酸化JNK表达减少，12小时增加至接近正常水平，然后在24小时呈下降趋势。Pearson线性相关分析显示p-Akt表达与凋亡细胞数呈负相关。这些结果表明，Akt的激活可能是脊髓缺血后神经元凋亡延迟的关键因素，特别是在再灌注阶段，因此可能是脊髓损伤后神经元保护和减少神经元凋亡的靶点。
The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.