Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

Nobutoshi Morimoto; Makiko Nagai; Yasuyuki Ohta; Kazunori Miyazaki; Tomoko Kurata; Mizuki Morimoto; Tetsuro Murakami; Yasushi Takehisa; Yoshio Ikeda; Tatsushi Kamiya; Koji Abe

doi:10.1016/j.brainres.2007.06.045

Increased autophagy in transgenic mice with a G93A mutant SOD1 gene

Brain Res. 2007 Sep 5:1167:112-7. doi: 10.1016/j.brainres.2007.06.045. Epub 2007 Jul 7.

Authors

Nobutoshi Morimoto¹, Makiko Nagai, Yasuyuki Ohta, Kazunori Miyazaki, Tomoko Kurata, Mizuki Morimoto, Tetsuro Murakami, Yasushi Takehisa, Yoshio Ikeda, Tatsushi Kamiya, Koji Abe

Affiliation

¹ Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.

PMID: 17689501
DOI: 10.1016/j.brainres.2007.06.045

Abstract

Autophagy, like the ubiquitin-proteasome system, is considered to play an important role in preventing the accumulation of abnormal proteins. Rat microtubule-associated protein 1 light chain 3 (LC3) is important for autophagy, and the conversion from LC3-I into LC3-II is accepted as a simple method for monitoring autophagy. We examined a SOD1G93A transgenic mouse model for amyotrophic lateral sclerosis (ALS) to consider a possible relationship between autophagy and ALS. In our study we analyzed LC3 and mammalian target of rapamycin (mTOR), a suppressor of autophagy, by immunoassays. The level of LC3-II, which is known to be correlated with the extent of autophagosome formation, was increased in SOD1G93A transgenic mice at symptomatic stage compared with non-transgenic or human wild-type SOD1 transgenic animals. Moreover, the ratio of phosphorylated mTOR/Ser2448 immunopositive motor neurons to total motor neurons was decreased in SOD1G93A-Tg mice. The present data show the possibility of increased autophagy in an animal model for ALS. And autophagy may be partially regulated by an mTOR signaling pathway in these animals.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyotrophic Lateral Sclerosis / genetics
Amyotrophic Lateral Sclerosis / metabolism*
Amyotrophic Lateral Sclerosis / physiopathology
Animals
Autophagy / genetics*
Central Nervous System / metabolism
Central Nervous System / physiopathology
Disease Models, Animal
Female
Genetic Predisposition to Disease / genetics
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microtubule-Associated Proteins / metabolism
Motor Neurons / metabolism
Mutation / genetics
Nerve Degeneration / genetics
Nerve Degeneration / metabolism*
Nerve Degeneration / physiopathology
Nerve Tissue Proteins / metabolism
Phosphorylation
Protein Kinases / analysis
Protein Kinases / metabolism*
Serine / metabolism
Spinal Cord / metabolism
Spinal Cord / physiopathology
Superoxide Dismutase / genetics*
Superoxide Dismutase-1
TOR Serine-Threonine Kinases
Up-Regulation / physiology

Substances

Map1lc3b protein, mouse
Microtubule-Associated Proteins
Nerve Tissue Proteins
SOD1 protein, human
Serine
Sod1 protein, mouse
Sod1 protein, rat
Superoxide Dismutase
Superoxide Dismutase-1
Protein Kinases
MTOR protein, human
mTOR protein, mouse
mTOR protein, rat
TOR Serine-Threonine Kinases