Proteomic analysis for protein carbonyl as an indicator of oxidative damage in senescence-accelerated mice.
The senescence-accelerated prone mouse strain 8 (SAMP8) exhibits a remarkable age-accelerated deterioration in learning and memory. In this study, we identified carbonyl modification, a marker of protein oxidation, in liver and brain of SAMP8 from peptide mass fingerprints using MALDI-TOF mass spectrometry in combination with LC-MS/MS analysis. Carbonyl modification of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in liver at 3 month and hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp) in brain at 9 month were higher in SAMP8 compared with control SAMR1. We demonstrated carbonyl modification of purified Cu,Zn-SOD increased by the reaction with H2O2. Therefore, progressive accumulation of oxidative damage to Cu,Zn-SOD, may cause dysfunction of defense systems against oxidative stress in SAMP8 with a higher oxidative states, leading to acceleration of aging. Furthermore, carbonyl modification of HCNP-pp may be involved in pathophysiological alterations associated with deterioration in the learning and memory in the brain seen in SAMP8.
Nabeshi
Hiromi
H
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan.
Oikawa
Shinji
S
Inoue
Sumiko
S
Nishino
Kohsuke
K
Kawanishi
Shosuke
S
D000375:Aging; D000818:Animals; D002244:Carbon / Q000737:chemistry*; D016922:Cellular Senescence; D015180:Electrophoresis, Gel, Two-Dimensional; D006624:Hippocampus / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry; D007858:Learning; D008297:Male; D008568:Memory; D051379:Mice; D018384:Oxidative Stress; D040901:Proteomics / Q000379:methods*; D017382:Reactive Oxygen Species; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017382:Reactive Oxygen Species; D002244:Carbon; D006861:Hydrogen Peroxide