虚血再灌流サル海馬における酸化損傷タンパク質の同定

抄録

Oxidative stress during ischemia-reperfusion is thought to be a major cause of brain injury. It has been reported that reactive oxygen species (ROS) causes extensive cell death in the cornu ammonis (CA) 1 region but not in the remaining CA2-4 region and dentate gyrus (DG) of the hippocampus, which is known to be involved in learning and memory processes. In this study, to identify and characterize carbonyl-modified proteins, protein oxidation products, in hippocampal CA1 region isolated from Japanese monkeys after transient cerebral ischemia-reperfusion, we performed two-dimensional gel electrophoresis with immunochemical detection of protein carbonyls (2D Oxyblot) and two-dimensional differential in-gel electrophoretic analysis (2D DIGE). Using 2D Oxyblot analysis, we demonstrated for the first time that carbonyl modification of heat shock 70 kDa protein 1 (Hsp70-1), a member of Hsp70 family, in CA1 region was extensively increased prior to the neuronal cell death induced by ischemic-reperfusion insult. Hsp70 molecular chaperones are known to be induced by oxidative stress and have neuroprotective function. Therefore, we considered that ischemia-reperfusion-induced oxidative damage to Hsp70-1 in CA1 region may lead to loss of the neuroprotective function, which contributes to neuronal cell death.