Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid protein and myelin basic protein genes in rat spinal cord injury
Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid protein and myelin basic protein genes in rat spinal cord injury
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DOI：
10.1016/s0891-0618(03)00044-9
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发表时间：
2003-10-01
影响因子：
2.8
通讯作者：
Banik, NL
中科院分区：
文献类型：
--
作者：
Ray, SK;Matzelle, DD;Banik, NL
脊髓损伤（SCI）与进行性神经变性和功能障碍有关。这种发病机制涉及多种细胞和分子机制。特别是，创伤后蛋白酶的激活可导致脊髓细胞凋亡。钙蛋白酶是一种钙依赖性半胱氨酸蛋白酶，在创伤后细胞凋亡中发挥重要作用。我们通过减重诱导大鼠 SO（40 g-cm 力）24 小时后，在五个 1 厘米长的脊髓节段（S1，远端吻端；S2，近端端；S3，病变；S4，近尾端；S5，远端尾端）中发现了凋亡和蛋白脂质蛋白（PLP）和髓磷脂碱性蛋白（MBP）基因转录的减少 方法。假手术大鼠接受了椎板切除术并且没有受到损伤。损伤大鼠的病灶（S3）处发生明显的核小体间DNA断裂，近节段（S2和S4）中度发生，远节段（S1和S5）轻微发生，表明病灶和半暗带发生细胞凋亡。 PLP 和 MBP 的转录水平在病变中显着降低，在附近节段中适度降低，表明细胞凋亡损失损害了髓磷脂两种重要结构成分的生物合成。立即给予受伤大鼠钙蛋白酶抑制剂 E-64-d (1 mg/kg) 可防止细胞凋亡并恢复这些基因的转录，表明钙蛋白酶抑制剂对治疗 SCI 具有治疗功效。 (C) 2003 Elsevier B.V. 保留所有权利。
Spinal cord injury (SCI) is associated with progressive neurodegeneration and dysfunction. Multiple cellular and molecular mechanisms are involved in this pathogenesis. In particular, the activation of proteases following trauma can cause apoptosis in the spinal cord. Calpain, a calcium-dependent cysteine protease, plays a major role in apoptosis following trauma. We identified apoptosis and decrease in transcription of the genes for proteolipid protein (PLP) and myelin basic protein (MBP) in five 1-cm long spinal cord segments (S1, distant rostral; S2, near rostral; S3, lesion; S4, near caudal; and S5, distant caudal) 24 h after induction of SO (40 g-cm force) in rats by weight-drop method. Sham rats underwent laminectomy and did not receive injury. Internucleosomal DNA fragmentation occurred prominently in the lesion (S3), moderately in near segments (S2 and S4), and slightly in distant segments (S1 and S5) of injured rats, indicating the occurrence of apoptosis in the lesion and penumbra. Levels of transcription of PLP and MBP were reduced highly in the lesion and moderately in near segments, suggesting that apoptotic loss of cells impaired biosynthesis of two important structural components of myelin. Immediate administration of the calpain inhibitor E-64-d (1 mg/kg) to injured rats prevented apoptosis and restored transcription of these genes, indicating the therapeutic efficacy of calpain inhibitor for treatment of SCI. (C) 2003 Elsevier B.V. All rights reserved.