Sustained induction of survival p-AKT and p-ERK signals after transient hypoxia in mice spinal cord with G93A mutant human SOD1 protein

Hristelina Ilieva, Isao Nagano, Tetsuro Murakami, Mito Shiote, Mikio Shoji, Koji Abe

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Expression of survival p-AKT and p-ERK signals was examined by immunohistochemistry and Western blotting in the lumbar spinal cord of 12-week-old presymptomatic mice with human mutant G93A SOD1 gene (transgenic, Tg) and their wild-type (Wt) littermates during normoxia, and 0 and 6 h after 2 h of 9% hypoxia. During normoxia, a stronger p-AKT signal was detected in the nucleus of the motor neurons of Tg animals. At 0 h of recovery from 2 h of hypoxia, both p-AKT and p-ERK signals were induced at a slightly lower level in Tg (1.1-1.2-fold) compared to those of Wt (1.2-1.5-fold) animals. At 6 h of recovery, both p-AKT and p-ERK signals were sustained in the lumbar spinal motor neurons of Tg animals, while those in Wt animals quickly returned to baseline level. As a control, at 6 h of recovery, the hippocampus of Tg animals showed significantly sustained p-AKT levels, but not p-ERK levels, compared to Wt. The current results suggest that the presence of mutant SOD1 alters survival p-AKT and p-ERK signals, possibly to compensate for the acquired gain-of-function of the mutant protein.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalJournal of the Neurological Sciences
Volume215
Issue number1-2
DOIs
Publication statusPublished - Nov 15 2003

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Genetically Modified Animals
Spinal Cord
Motor Neurons
Survival
Wild Animals
Mutant Proteins
Hippocampus
Western Blotting
Immunohistochemistry
Genes
human SOD1 protein
Hypoxia

Keywords

  • Amyotrophic lateral sclerosis (ALS)
  • Hypoxia
  • Phosphorylated extracellular signal-regulated kinase (p-ERK)
  • Phosphorylated serine/ threonine kinase AKT (p-AKT)
  • Superoxide dismutase 1 (SOD1)

ASJC Scopus subject areas

  • Ageing
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

Sustained induction of survival p-AKT and p-ERK signals after transient hypoxia in mice spinal cord with G93A mutant human SOD1 protein. / Ilieva, Hristelina; Nagano, Isao; Murakami, Tetsuro; Shiote, Mito; Shoji, Mikio; Abe, Koji.

In: Journal of the Neurological Sciences, Vol. 215, No. 1-2, 15.11.2003, p. 57-62.

Research output: Contribution to journalArticle

Ilieva, Hristelina ; Nagano, Isao ; Murakami, Tetsuro ; Shiote, Mito ; Shoji, Mikio ; Abe, Koji. / Sustained induction of survival p-AKT and p-ERK signals after transient hypoxia in mice spinal cord with G93A mutant human SOD1 protein. In: Journal of the Neurological Sciences. 2003 ; Vol. 215, No. 1-2. pp. 57-62.
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