Jordán Joaquín, Galindo María F, Tornero Daniel, González-García Carmen, Ceña Valentín
Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Albacete, Spain.
J Neurochem. 2004 Apr;89(1):124-33. doi: 10.1046/j.1471-4159.2003.02299.x.
Apoptosis is an active process that is regulated by different signalling pathways. One of the more important organelles involved in apoptosis regulation is the mitochondrion. Electron chain transport disruption increases free radical production leading to multiple conductance channel opening, release of cytochrome c and caspase activation. This death pathway can be blocked by anti-apoptotic members of the Bcl-2 protein family that might shift redox potential to a more reduced state, preventing free radical-mediated damage. 6-Hydroxydopamine (6-OHDA) has been widely used to generate Parkinson's disease-like models. It is able to generate free radicals and to induce catecholaminergic cell death. In this paper we have used the human neuroblastoma cell line SH-SY5Y overexpressing Bcl-x(L) as a model to gain insights into the mechanisms through which Bcl-x(L) blocks 6-OHDA-induced cell death and to identify the molecular targets for this action. Herein, we present evidence supporting that the Bcl-x(L)-anti-apoptotic signal pathway seems to prevent mitochondrial multiple conductance channel opening, cytochrome c release and caspase-3 like activity following 6-OHDA treatment in the human neuroblastoma cell line SH-SY5Y.
细胞凋亡是一个由不同信号通路调控的主动过程。参与细胞凋亡调控的较为重要的细胞器之一是线粒体。电子链传输中断会增加自由基的产生，导致多个电导通道开放、细胞色素c释放和半胱天冬酶激活。这条死亡途径可被Bcl-2蛋白家族的抗凋亡成员阻断，这些成员可能将氧化还原电位转变为更还原的状态，从而防止自由基介导的损伤。6-羟基多巴胺（6-OHDA）已被广泛用于建立帕金森病样模型。它能够产生自由基并诱导儿茶酚胺能细胞死亡。在本文中，我们使用过表达Bcl-x(L)的人神经母细胞瘤细胞系SH-SY5Y作为模型，以深入了解Bcl-x(L)阻断6-OHDA诱导的细胞死亡的机制，并确定这一作用的分子靶点。在此，我们提供证据支持，在人神经母细胞瘤细胞系SH-SY5Y中，Bcl-x(L)抗凋亡信号通路似乎可防止6-OHDA处理后线粒体多个电导通道开放、细胞色素c释放及半胱天冬酶-3样活性。
