The hippocampal proteomic analysis of senescence-accelerated mouse: implications of Uchl3 and mitofilin in cognitive disorder and mitochondria dysfunction in SAMP8.
Senescence-accelerated mouse prone 8 (SAMP8) is considered as a useful animal model for age-related learning and memory impairments. Hippocampus, a critical brain region associated with cognitive decline during normal aging and various neurodegenerative diseases, appeared a series of abnormalities in SAMP8. To investigate the molecular mechanisms underlying age-related cognitive disorders, we used 2-DE coupled with MALDI TOF/TOF MS to analyze the differential protein expression of the hippocampus of SAMP8 at 6-month-old compared with the age-matched SAM/resistant 1 (SAMR1) which shows normal aging process. Two proteins were found to be markedly changed in SAMP8 as compared to SAMR1: ubiquitin carboxyl-terminal hydrolase L3 (Uchl3), implicating in cytosolic proteolysis of oxidatively damaged proteins, was down-regulated while mitofilin, a vital protein for normal mitochondria function, exhibited four isoforms with a consistent basic shift of isoelectric point among the soluble hippocampal proteins in SAMP8 compared with SAMR1. The alterations were confirmed by Western blotting analysis. The analysis of their expression changes may shed light on the mechanisms of learning and memory deficits and mitochondrial dysfunction as observed in SAMP8.
Wang
Qingsong
Q
The National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, 100871, PR China.
Liu
Yashu
Y
Zou
Xiao
X
Wang
Qian
Q
An
Mingrui
M
Guan
Xin
X
He
Jintang
J
Tong
Yuanpeng
Y
Ji
Jianguo
J
D000375:Aging / Q000502:physiology*; D000818:Animals; D003072:Cognition Disorders / Q000503:physiopathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C526917:UCHL3 protein, mouse; C532603:mitofilin protein, mouse; D043222:Ubiquitin Thiolesterase