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首页> 外文期刊>Glia >Proteasome inhibition suppresses schwann cell dedifferentiation in vitro and in vivo
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Proteasome inhibition suppresses schwann cell dedifferentiation in vitro and in vivo

机译：蛋白酶体抑制在体外和体内抑制雪旺细胞去分化

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The ubiquitin-proteasome system (UPS), lysosomes, and autophagy are essential protein degradation systems for the regulation of a variety of cellular physiological events including the cellular response to injury. It has recently been reported that the UPS and autophagy mediate the axonal degeneration caused by traumatic insults and the retrieval of nerve growth factors. In the peripheral nerves, axonal degeneration after injury is accompanied by myelin degradation, which is tightly related to the reactive changes of Schwann cells called dedifferentiation. In this study, we examined the role of the UPS, lysosomal proteases, and autophagy in the early phase of Wallerian degeneration of injured peripheral nerves. We found that nerve injury induced an increase in the ubiquitin conjugation and lysosomal-associated membrane protein-1 expression within 1 day without any biochemical evidence for autophagy activation. Using an ex vivo explant culture of the sciatic nerve, we observed that inhibiting proteasomes or lysosomal serine proteases prevented myelin degradation, whereas this was not observed when inhibiting autophagy. Interestingly, proteasome inhibition, but not leupeptin, prevented Schwann cells from inducing dedifferentiation markers such as p75 nerve growth factor receptor and glial fibrillary acidic protein in vitro and in vivo. In addition, proteasome inhibitors induced cell cycle arrest and cellular process formation in cultured Schwann cells. Taken together, these findings indicate that the UPS plays a role in the phenotype changes of Schwann cells in response to nerve injury.
机译：泛素-蛋白酶体系统（UPS），溶酶体和自噬是必需的蛋白质降解系统，用于调节多种细胞生理事件，包括细胞对损伤的反应。最近有报道说，UPS和自噬介导了由创伤性损伤和神经生长因子的恢复引起的轴突变性。在周围神经中，损伤后的轴突变性伴随着髓磷脂降解，髓鞘降解与雪旺氏细胞的反应性变化紧密相关，称为去分化。在这项研究中，我们检查了UPS，溶酶体蛋白酶和自噬在受伤的周围神经的沃勒变性早期的作用。我们发现神经损伤在1天之内诱导了泛素结合和溶酶体相关膜蛋白1表达的增加，而没有任何自噬激活的生化证据。使用坐骨神经的离体外植体培养物，我们观察到抑制蛋白酶体或溶酶体丝氨酸蛋白酶可防止髓磷脂降解，而当抑制自噬时则未观察到。有趣的是，在体外和体内，蛋白酶体的抑制作用而不是亮肽素的作用阻止了雪旺氏细胞诱导去分化标记，例如p75神经生长因子受体和神经胶质纤维酸性蛋白。另外，蛋白酶体抑制剂在培养的雪旺氏细胞中诱导细胞周期停滞和细胞过程形成。综上所述，这些发现表明UPS在响应神经损伤的雪旺细胞表型变化中起作用。

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