脑红蛋白通过抑制细胞死亡的内在途径保护神经细胞免于凋亡
Neuroglobin protects nerve cells from apoptosis by inhibiting the intrinsic pathway of cell death
摘要：
在过去的几年中，大量证据表明，高水平表达的神经红蛋白蛋白在体外、动物模型和人体中保护神经元，使其免受与缺氧和淀粉样蛋白损伤相关的细胞死亡。然而，到目前为止，脑红蛋白的保护作用的确切机制尚未确定。使用细胞生物学和生物化学方法，我们证明，脑红蛋白抑制细胞凋亡的内在途径，在体外和干预激活的半胱天冬酶9通过与细胞色素c的相互作用。使用系统水平的信息的细胞凋亡信号传导反应，我们已经开发了一个定量模型的神经红蛋白抑制细胞凋亡，它模拟在单细胞水平上的神经红蛋白阻断的巨噬细胞形成。此外，该模型使我们能够在实验研究不易获得的条件下探索脑红蛋白的作用。我们发现脑红蛋白对神经元的保护作用是非常浓度敏感的。脑红蛋白的影响可能来自其与细胞色素c的结合及其随后的氧化还原反应，尽管单独的结合足以阻断胱天蛋白酶9原的活化。这些数据提供了一个解释的作用，脑红蛋白在保护神经细胞免受不必要的凋亡。
英文摘要：
In the past few years, overwhelming evidence has accrued that a high level of expression of the protein neuroglobin protects neurons in vitro, in animal models, and in humans, against cell death associated with hypoxic and amyloid insult. However, until now, the exact mechanism of neuroglobin's protective action has not been determined. Using cell biology and biochemical approaches we demonstrate that neuroglobin inhibits the intrinsic pathway of apoptosis in vitro and intervenes in activation of pro-caspase 9 by interaction with cytochrome c. Using systems level information of the apoptotic signalling reactions we have developed a quantitative model of neuroglobin inhibition of apoptosis, which simulates neuroglobin blocking of apoptosome formation at a single cell level. Furthermore, this model allows us to explore the effect of neuroglobin in conditions not easily accessible to experimental study. We found that the protection of neurons by neuroglobin is very concentration sensitive. The impact of neuroglobin may arise from both its binding to cytochrome c and its subsequent redox reaction, although the binding alone is sufficient to block pro-caspase 9 activation. These data provides an explanation the action of neuroglobin in the protection of nerve cells from unwanted apoptosis.
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