Laminin chain expression suggests that laminin-10 is a major isoform in the mouse hippocampus and is degraded by the tissue plasminogen activator/plasmin protease cascade during excitotoxic injury
Laminin chain expression suggests that laminin-10 is a major isoform in the mouse hippocampus and is degraded by the tissue plasminogen activator/plasmin protease cascade during excitotoxic injury
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DOI：
10.1016/s0306-4522(02)00704-2
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Strickland, S
中科院分区：
文献类型：
--
作者：
Indyk, JA;Chen, ZL;Strickland, S
层粘连蛋白是细胞外基质的重要组成部分，参与神经元的发育、存活和再生。组织纤溶酶原激活物/纤溶酶细胞外蛋白酶级联反应和下游层粘连蛋白降解与兴奋性毒素诱导的神经元变性有关。为了确定哪些特定的层粘连蛋白链参与，我们研究了海马中层粘连蛋白的表达，以及表达它们的细胞类型。逆转录-PCR结果表明，所有层粘连蛋白链的信使RNA可以检测到海马。为了确定层粘连蛋白链表达的定位，使用免疫染色。该方法表明，α 5、β 1和γ 1在神经元细胞层中表达最高。免疫印迹证实海马表达的链α 5，β 1和γ 1，和RNA原位杂交显示的α 5，β 1和γ 1的神经元表达模式。在海马内注射红藻氨酸后的早期时间点，α 5，β 1和γ 1链免疫反应丧失。此外，组织纤溶酶原激活物缺陷小鼠对海人藻酸盐诱导的神经元死亡具有抵抗力，在海马内注射海人藻酸盐后，层粘连蛋白α 5、β 1和γ 1没有显著变化。（α 5-β 1-γ 1）包含小鼠海马中的主要神经元层粘连蛋白，并在兴奋性毒性损伤期间神经元死亡之前通过组织纤溶酶原激活剂/纤溶酶蛋白酶级联降解。通过鉴定参与兴奋性毒性损伤后神经元变性的神经元层粘连蛋白（层粘连蛋白-10），本研究阐明了海马细胞外基质的分子定义，并进一步定义了神经元死亡机制的途径。(C)2003年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Laminins are important components of the extracellular matrix, and participate in neuronal development, survival and regeneration. The tissue plasminogen activator/ plasmin extracellular protease cascade and downstream laminin degradation are implicated in excitotoxin-induced neuronal degeneration. To determine which specific laminin chains are involved, we investigated the expression of laminins in the hippocampus, and the cell types expressing them. Reverse transcription-PCR demonstrated that the messenger RNAs for all laminin chains could be detected in the hippocampus. To determine the localization of laminin chain expression, immunostaining was used. This method showed that alpha5, beta1 and gamma1 are most highly expressed in the neuronal cell layers. Immunoblotting confirmed the hippocampal expression of the chains alpha5, beta1 and gamma1, and RNA in situ hybridization showed a neuronal expression pattern of alpha5, beta1 and gamma1. At early time points following intrahippocampal injection of kainate, alpha5, beta1 and gamma1 chain immunoreactivities were lost. In addition, tissue plasminogen activator-deficient mice, which are resistant to kainate-induced neuronal death, show no significant change in laminins alpha5, beta1 and gamma1 after intrahippocampal kainate injection.Taken together, these results suggest that laminin-10 (alpha5-beta1-gamma1) comprises a major neuronal laminin in the mouse hippocampus, and is degraded before neuronal death during excitotoxic injury by the tissue plasminogen activator/plasmin protease cascade. By identifying a neuronal laminin (laminin-10) that participates in neuronal degeneration after excitotoxic injury, this study clarifies the molecular definition of the extracellular matrix in the hippocampus and further defines a pathway for mechanisms of neuronal death. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.