title: Protection of vincristine-induced neuropathy by WldS expression and the independence of the activity of Nmnat1.
abstract: The slow Wallerian degeneration protein (WldS), a fusion protein containing amino-terminal E4B and full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays axon degeneration caused by physical damages, toxins and genetic mutations which result in patients being diagnosed with neurodegenerative diseases. It is still controversial whether the suppression of axonal degeneration by WldS is due to Nmnat1 or other portion. We generated WldS or Nmnat1-overexpressing Neuro2A cell lines, in which neuronal differentiation including neurite elongation can be induced by retinoic acid. The overexpression of WldS delayed the neurite degeneration by vincristine, whereas that of Nmnat1 did not delay it much. Taken together, Nmnat1 is considerably weaker than WldS for protection from toxic injury in vitro, suggesting that amino-terminal region of WldS is likely to be more significant for protection from axonal degeneration.
authors.affiliation: Department of Molecular Biochemistry, Hokkaido University Graduate School of Medicine, N15, W7 Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Tsukiyama
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004347:Drug Interactions; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000378:metabolism*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014750:Vincristine / Q000633:toxicity*
chemical_list: D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D014212:Tretinoin; D014750:Vincristine; C442580:Wld protein, mouse; C510972:Nmnat1 protein, mouse