Proteome analysis in hippocampus of mice overexpressing human Cu/Zn-superoxide dismutase 1.
Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in metabolism of oxygen free radicals and oxidative stress. Transgenic mice overexpressing human SOD1 (Tg-hSOD1) are useful model for Down syndrome (trisomy 21) and familial amyotrophic lateral sclerosis (ALS). It was shown recently that Tg-hSOD1 mice develop a characteristic set of neurodegenerative changes in hippocampus and we therefore decided to study differential protein expression patterns, constructing a mouse hippocampal proteome map using two-dimensional electrophoresis (2-DE) with in-gel digestion of spots followed by matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) identification and quantitatively compared protein profiles between non-transgenic mice, hemizygous and homozygous Tg-hSOD1 mice. In total 1056 spots were analysed, resulting in the identification of 445 polypeptides that were the products of 157 different genes. Among these a series of proteins involved in scaffolding, metabolism, signaling and other functions were deranged. Our findings suggest that overexpressed SOD1 directly or by generating reactive oxygen species may lead to aberrant protein expressional patterns that in turn may lead to or reflect neurodegeneration observed in this animal model.
Shin
Joo-Ho
JH
Department of Pediatrics, Medical University of Vienna, Wahringer Gurtel 18-20, 1090 Vienna, Austria.
London
Jacqueline
J
Le Pecheur
Marie
M
Weitzdoerfer
Rachel
R
Hoeger
Harald
H
Lubec
Gert
G
D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000201:enzymology / Q000503:physiopathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology*; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D020543:Proteome; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase