Axonal protection by modulation of p62 expression in TNF-induced optic nerve degeneration

NEUROSCIENCE LETTERS

卷:581

Article

Kojima, Kaori¹  Kitaoka, Yasushi^1,2  Munemasa, Yasunari¹  Hirano, Ayano¹  Sase, Kana¹  Takagi, Hitoshi¹ 

[1] St Marianna Univ, Sch Med, Dept Ophthalmol, Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan

[2] St Marianna Univ, Grad Sch Med, Dept Mol Neurosci, Miyamae Ku, Kawasaki, Kanagawa 2168511, Japan

关键词: p62;    Rapamycin;    Autophagy;    Tumor necrosis factor;    Optic nerve;   

DOI  :  10.1016/j.neulet.2014.08.021

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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