Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

Oxidative Stress and FGF-1 Release from Astrocytes

Jin-ichi Ito*,Jiansheng Gong,Makoto Michikawa

The brain is an organ to consume highly oxygen and to produce Reactive Oxygen Species (ROS) at high level. ROS facilitate to produce many kinds of peroxide lipids in the lipid-rich brain. Accordingly, it is considered that the brain is an organ to undergo easily oxidative stress. Severe diseases of brain such as Parkinsonism and Alzheimer’s disease are seemingly accompanied with oxidative stress. The construction of protection system against oxidative stress is very important to maintain normal neuron function in the brain. We are studying the production and function of Fibroblast Growth Factor 1 (FGF-1) in astrocytes undergoing oxidative stress. Astrocytes increase FGF-1 release under stressful condition such as oxidative stress and long-term cultured stress. In vitro treatment of rat astrocytes with 100 μM Hydrogen Peroxide (H2O2) for 10 min enhances the release of FGF-1 along with cytosolic proteins such as HSP90, HSP70, PK-Cδ without inducing apoptosis. The treatment with H2O2 enhanced the flow into the cells of exogenous compounds such as trypsin and Rhodamin-phalloidin also, suggesting increase in permeability of plasma membrane in astrocytes treated with H2O2. Oxidative stress suppressed transiently cholesterol synthesis and enhanced cholesterol release from the cell surface, resulted in impairment of the cholesterol metabolism. The change of cholesterol metabolism may participate in the increase in membrane permeability in astrocytes undergone oxidative stress. FGF-1 released from rat astrocytes enhances apoE-containing HDL-like lipoproteins (apoE/HDL) generation of astrocytes in the manner of autocrine action. In this review, we describe physiological significance of FGF-1 released from astrocytes stimulated by oxidative stress to relate with generation of apoE/HDL of astrocytes in the brain.