Involvement of β1 integrin in βAP-induced apoptosis in human neuroblastoma cells
Involvement of β1 integrin in βAP-induced apoptosis in human neuroblastoma cells
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DOI：
10.1016/j.mcn.2003.09.008
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发表时间：
2004-01-01
影响因子：
3.5
通讯作者：
Canonico, PL
中科院分区：
文献类型：
--
作者：
Bozzo, C;Lombardi, G;Canonico, PL
整合素介导的细胞粘附是细胞存活和分化所必需的。最近，整合素已被提出作为β-淀粉样肽（β AP）神经毒性的靶点。我们在此报道了用β AP（1-42）或活性β AP片段（25-35）处理在SK-N-BE和SH-SY 5 Y细胞系中诱导大量凋亡。在胶原I度、纤连蛋白或层粘连蛋白存在下，β AP毒性严重降低。这种保护作用似乎是由整联蛋白介导的，因为神经母细胞瘤细胞与针对β（1）和α（1）整联蛋白亚基的抗体预孵育大大增强了β AP诱导的凋亡。此外，用β AP处理诱导质膜中表达的整合素亚基β（1）和α（1）的强烈减少，这发生在处理后3小时，在凋亡形态出现之前。α 1 β 1整合素的快速下调在β AP处理后15-24 μ l几乎完全恢复，放线菌酮不能阻止。总之，我们的数据表明β AP神经毒性和α 1 β 1整合素表达调节之间的关系，并支持整合素功能异常可能在β AP介导的神经毒性中起重要作用的假设。(C)2003年爱思唯尔公司All rights reserved.
Integrin-mediated cell adhesion is required for cell survival and differentiation. Recently, integrins have been proposed as a target for beta-amyloid peptide (betaAP) neurotoxicity. We report here that treatment with betaAP (1-42) or with the active betaAP fragment (25-35) induced a great deal of apoptosis in SK-N-BE and SH-SY5Y cell lines. In the presence of either collagen Idegrees, fibronectin, or laminin, betaAP toxicity was severely reduced. This protective effect seems to be mediated by integrins, because preincubation of neuroblastoma cells with antibodies directed against beta(1) and alpha(1) integrin subunits greatly enhanced betaAP-induced apoptosis. In addition, treatment with betaAP induced a strong reduction of beta(1) and alpha(1), integrin subunits expressed in plasma membrane, which occurred 3 h after treatment, before the appearance of the apoptotic morphology. The rapid downregulation of the alpha(1)beta(1) integrin was almost completely recovered 15-24 It after betaAP treatment and was not prevented by cycloheximide. In conclusion, our data indicate a relationship between betaAP neurotoxicity and modulation of alpha(1)beta(1), integrin expression, and support the hypothesis that aberrant integrin function may play a significant role in betaAP-mediated neurotoxicity. (C) 2003 Elsevier Inc. All rights reserved.