Knockdown of integrin β4 in primary cultured mouse neurons blocks survival and induces apoptosis by elevating NADPH oxidase activity and reactive oxygen species level
Knockdown of integrin β4 in primary cultured mouse neurons blocks survival and induces apoptosis by elevating NADPH oxidase activity and reactive oxygen species level
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DOI：
10.1016/j.biocel.2007.10.006
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Miao, Junying
中科院分区：
文献类型：
--
作者：
Lv, Xin;Su, Le;Miao, Junying
最近，整合素β 4在驱动病理性血管生成和肿瘤进展的信号网络中的特定作用已被揭示。我们前期的研究表明整合素β 4可能参与神经元存活信号转导。为了进一步研究整合素β 4在原代培养小鼠神经元存活和凋亡中的作用，我们通过其特异性小干扰RNA抑制整合素β 4的表达。细胞活力显著下降，神经元发生凋亡，整合素β 4下调。接下来，我们研究了siRNA介导的整合素β 4下调对细胞内活性氧水平以及NADPH氧化酶和超氧化物歧化酶活性的影响。神经元内活性氧水平显著升高，锰依赖性超氧化物歧化酶和铜/锌依赖性超氧化物歧化酶活性无明显变化，但NADPH氧化酶活性升高。此外，NADPH氧化酶的特异性抑制剂二苯碘季铵盐氯化物抑制NADPH氧化酶减弱了整合素β 4敲低诱导的神经元死亡。这些数据表明，整合素β 4是神经元存活和凋亡的关键因素，并表明该整合素亚基可能通过调节NADPH氧化酶和活性氧水平在神经元存活和凋亡中发挥作用。(C)2007爱思唯尔有限公司保留所有权利。
Recently, the specific roles of integrin beta 4 in the signaling networks that drive pathological angiogenesis and tumor progression have been revealed. Our previous study showed that integrin beta 4 might be involved in neuron survival signal transduction. To further our study on the role of integrin beta 4 in the survival and apoptosis of primary cultured mouse neurons, we inhibited the expression of integrin beta 4 by its specific small interfering RNA. Viability of the cells remarkably declined, and neurons underwent apoptosis with down-regulation of integrin beta 4. Next, we investigated the effect of siRNA-mediated down-regulation of integrin beta 4 on the level of intracellular reactive oxygen species and the activities of NADPH oxidase and superoxide dismutase. The level of reactive oxygen species in the neurons was elevated significantly, the activities of manganese-dependent superoxide dismutase and copper/zinc-dependent superoxide dismutase were not altered, but the activity of NADPH oxidase was increased. Furthermore, inhibition of NADPH oxidase by its specific inhibitor dibenziodolium chloride attenuated the neuronal death induced by integrin beta 4 knockdown. The data suggest that integrin beta 4 is a key factor in neuron survival and apoptosis and indicate that this integrin subunit might perform its action through regulating NADPH oxidase and the level of reactive oxygen species in neuronal survival and apoptosis. (C) 2007 Elsevier Ltd. All rights reserved.