alpha-lipoic acid suppresses 6-hydroxydoparnine-induced ROS generation and apoptosis through the stimulation of glutathione synthesis but not by the expression of heme oxygenase-1

We previously reported that the generation of reactive oxygen species (ROS) is the initial event in cell death induced by 6-hydroxydopamine (6-OHDA), an experimental model of Parkinsonism. Since recent studies suggested the important role of antioxidant activity of alpha-lipoic acid (LA) in the suppression of apoptosis of various types, we studied the effect on 6-OHDA-induced apoptosis of PC12 cells. Biochemical analysis revealed that LA suppressed the 6-OHDA-induced ROS generation, increase of caspase-like activity and chromatin condensation. The suppression of 6-OHDA-induced apoptosis by LA required pre-incubation of PC12 cells with LA for 12-24 h. LA increased the intracellular levels of heme oxygenase-1 (HO-1) and glutathione (GSH) and stimulated the expression of GSH synthesis-related genes such as cystine/glutamate antiporter and gamma-glutamylcysteine synthetase (gamma-GCS). However, Sn-mesoporphyrin IX, an inhibitor of HO-1, did not attenuate the LA-induced suppression of apoptosis. In contrast, buthionine sulfoximine, an inhibitor of gamma-GCS, attenuated the LA-induced suppression of ROS generation and chromatin condensation. in addition, a transcription factor Nrf2, which regulates the expression of antioxidant enzymes such as gamma-GCS, translocated to the nucleus by LA. These results suggested that LA suppressed the 6-OHDA induced-apoptosis by the increase in cellular glutathione through stimulation of the GSH synthesis system but not by the expression of HO-1.</p

テイサアツ デ クドウ サレル リュウタイ ゾウフクキ ノ カイハツ

Today a structual material of an aircraft tends to use a nonmetal material like CFRP (carbon fiber reinforced plastic) in stead of metal material to save the weight. Then, the electronic control circuit is more affected by electromagnetic noise, thunder, radar and so on. We consider that it is useful to use optical control signal in stead of electrical control signal in such an environment. For this reason, it has been desired to realize an optical servo system. An optical servo system is a novel control servo system in which a part or all of the electric or electronic components of present control system are replaced with optical components in order to break through the limit of present electronic control system. We aim to develop the optical servo system using a photo-fluidic interface which converts optical control signal to pneumatic or hydraulic control signal. We had investigated the photo-fluidic interface theoretically and experimentally. And we developed the interface that the differential output pressure was proportional to input optical power. However, output fluid power from the interface is too low to drive an actuator directly. Therefore we need to develop a fluid booster amplifier driven by very low differential pressure. In this paper, we developed and tested two types of amplifier ; single and double acting booster amplifier. This amplifier consists of rubber film as a flapper and nozzle. We investigated their static and dynamic chracteristics. As a result, we found that the double acting booster amplifier was more useful to amplify very low differential pressure. This has following advantages. 1) Drift of zero output differential pressure is small because of a common flapper. 2) This type is less sensitive to the temperature change because it is operated by the difference of input pressure. To construct the optical servo system using this amplifier is our next future study