Nabeshi Hiromi, Oikawa Shinji, Inoue Sumiko, Nishino Kohsuke, Kawanishi Shosuke
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan.
Free Radic Res. 2006 Nov;40(11):1173-81. doi: 10.1080/10715760600847580.
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.
衰老加速易感性小鼠8品系（SAMP8）在学习和记忆方面表现出显著的年龄加速衰退。在本研究中，我们使用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）结合液相色谱-串联质谱（LC-MS/MS）分析，从肽质量指纹图谱中鉴定出衰老加速易感性小鼠8品系肝脏和大脑中蛋白质氧化的标志物羰基修饰。与对照品系SAMR1相比，3月龄SAMP8肝脏中的铜锌超氧化物歧化酶（Cu,Zn-SOD）和9月龄SAMP8大脑中的海马胆碱能神经刺激肽前体蛋白（HCNP-pp）的羰基修饰水平更高。我们证明，纯化的Cu,Zn-SOD与过氧化氢反应后羰基修饰增加。因此，在氧化状态较高的SAMP8中，Cu,Zn-SOD氧化损伤的逐渐积累可能导致抗氧化应激防御系统功能障碍，从而加速衰老。此外，HCNP-pp的羰基修饰可能参与了SAMP8中与大脑学习和记忆衰退相关的病理生理改变。
