title: Axonal protection by modulation of p62 expression in TNF-induced optic nerve degeneration.
abstract: 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.
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan; Department of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan. Electronic address: kitaoka@marianna-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaoka
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Munemasa
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sase
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takagi
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009901:Optic Nerve Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017208:Rats, Wistar; D000071456:Sequestosome-1 Protein; D020123:Sirolimus / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
chemical_list: D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D000071456:Sequestosome-1 Protein; C491079:Sqstm1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D020123:Sirolimus
keywords: Autophagy; Optic nerve; Rapamycin; Tumor necrosis factor; p62