Microglial secreted cathepsin B induces neuronal apoptosis
Microglial secreted cathepsin B induces neuronal apoptosis
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DOI：
10.1046/j.1471-4159.2001.00146.x
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发表时间：
2001-03-01
影响因子：
4.7
通讯作者：
Pocock, JM
中科院分区：
文献类型：
--
作者：
Kingham, PJ;Pocock, JM
活化的小胶质细胞释放出许多可以影响神经元信号传导和存活的物质。在这里，我们报告，小胶质细胞刺激肽嗜铬粒蛋白A（CGA），分泌半胱氨酸蛋白酶，组织蛋白酶B。CGA暴露的小胶质细胞的条件培养基对HT 22海马细胞系和小脑颗粒神经元的原代培养物具有神经毒性。在这两种神经元细胞类型中，神经毒性可以用z-FA-fetamine或通过用组织蛋白酶B抗体耗尽小胶质细胞条件培养基而显著减弱。条件培养基从激活的小胶质细胞或组织蛋白酶B单独诱导神经元凋亡和caspase 3激活。我们的数据表明，CGA激活的小胶质细胞可以触发神经元凋亡，这可能是通过分泌组织蛋白酶B介导的。由于组织蛋白酶也可能在淀粉样前体蛋白的淀粉样蛋白形成过程中发挥作用，这些结果可能对阿尔茨海默病神经病理学中的组织损伤和神经元损失具有重要意义。
Activated microglia release a number of substances that can influence neuronal signalling and survival. Here we report that microglia stimulated with the peptide chromogranin A (CGA), secreted the cysteine protease, cathepsin B. Conditioned medium from CGA exposed microglia was neurotoxic to the HT22 hippocampal cell line and to primary cultures of cerebellar granule neurones. In both neuronal cell types, the neurotoxicity could be significantly attenuated with z-FA-fmk or by depletion of microglial conditioned medium with cathepsin B antibody. Conditioned medium from activated microglia or cathepsin B alone induced neuronal apoptosis and caspase 3 activation. Our data indicate that CGA-activated microglia can trigger neuronal apoptosis and that this may be mediated through the secretion of cathepsin B. Since cathepsins may also play a role in the amyloidogenic processing of amyloid precursor protein, these results may have significance for tissue damage and neuronal loss in the neuropathology of Alzheimer's disease.