Axonal protection by modulation of p62 expression in TNF-induced optic nerve degeneration
Axonal protection by modulation of p62 expression in TNF-induced optic nerve degeneration
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DOI：
10.1016/j.neulet.2014.08.021
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发表时间：
2014-10-03
影响因子：
2.5
通讯作者：
Takagi, Hitoshi
中科院分区：
文献类型：
--
作者：
Kojima, Kaori;Kitaoka, Yasushi;Takagi, Hitoshi
p62，也称为隔离体1（SQSTM 1），在神经元细胞死亡中起关键作用。然而，p62在轴突变性中的作用仍不清楚。我们评估了p62表达的调节是否可能影响肿瘤坏死因子（TNF）诱导的视神经变性中的轴突丢失。免疫印迹分析表明，p62上调后，玻璃体内注射TNF的视神经。用p62小干扰RNA（siRNA）治疗对TNF诱导的轴突损失产生部分但显著的保护作用。雷帕霉素产生大量的轴突保护TNF注射后。我们发现p62 siRNA显著抑制了p62的增加。雷帕霉素治疗也显着抑制TNF诱导的p62蛋白水平的增加。这些结果表明，上调p62可能参与TNF诱导的轴突变性，降低p62水平可能导致轴突保护。(C)2014作者出版社：Elsevier爱尔兰Ltd.
p62, which is also called sequestosome 1 (SQSTM1), plays a critical role in neuronal cell death. However, the role of p62 in axonal degeneration remains unclear. We evaluated whether the modulation of p62 expression may affect axonal loss in tumor necrosis factor (TNF)-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with p62 small interfering RNA (siRNA) exerted a partial but significant protective effect against TNF-induced axonal loss. Rapamycin exerted substantial axonal protection after TNF injection. We found that the increase in p62 was significantly inhibited by p62 siRNA. Treatment with rapamycin also significantly inhibited increased p62 protein levels induced by TNF. These results suggest that the upregulation of p62 may be involved in TNF-induced axonal degeneration and that decreased p62 levels may lead to axonal protection. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.