Sustained induction of survival p-AKT and p-ERK signals after transient hypoxia in mice spinal cord with G93A mutant human SOD1 protein.
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.
Department of Neurology, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, 700-8558 Okayama, Japan.
Hristelina
H
Ilieva
Isao
I
Nagano
Tetsuro
T
Murakami
Mito
M
Shiote
Mikio
M
Shoji
Koji
K
Abe
D019943:Amino Acid Substitution / Q000235:genetics* / Q000502:physiology; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000201:enzymology* / Q000502:physiology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1
D011518:Proto-Oncogene Proteins; C000606290:SOD1 protein, human; C109415:SOD1 G93A protein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases