Co-Investigator(Kenkyū-buntansha) |
SHIMOHAMA Shun Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Professor, 医学部, 助教授 (60235687)
TANINO Hiroko Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Assistant, 薬学部, 助手 (90298688)
NAGASAWA Kazuki Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Assistant Lecturer, 薬学部, 講師 (30228001)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Research Abstract |
When oxidative stress is induced in the rat cerebral cortex through hyperoxia, the protein levels of phospholipase C (PLC)-β1 and -δ1 were significantly increased in the cerebral cortex, although that of PLC-γ1 was not altered. These results suggest that hyperoxia exerts oxidative stress on the rat cerebral cortex, and the protein levels of PLC-β1 and -δ1, but not PLC-γ1, were changed. Acrylonitrile (CAN) appears to induce astrocytomas through induction of oxidative stress on the rat brain selectively. Treatment of rats with CAN, but not hyperoxia, resulted in lipid peroxidation in the heart and cerebral cortex, and the effect on the latter was greater than on the former. In the CAN-treated cerebral cortex, significant increases in the PLC-β1 and -δ1 in the cytosol, and PLC-γ1 in the cytosolic and particulate fractions, and lysate were observed. In the rat heart, in which PLC-β1 could not be detected, PLC-γ1 and -δ1 were increased and decreased in the cytosolic and particulate fractions, respectively, by hyperoxia. In addition, the expression level of PLC-γ1 was decreased in the lysate by the treatment. In the heart treated with CAN, there was no change in the level of PLC-γ1, while PLC-δ1 was elevated in all fractions. We have demonstrated that oxidative stress induced by hyperoxia is apparently less than that induced by CAN administration in the heart as a peripheral tissue and the cerebral cortex as a central one. With both forms of oxidative stress, the protein levels of PLC isozymes were altered, but there was apparent difference in the altered protein levels between the different levels of oxidative stress, and between the organs. In order to obtain the information about contribution of PLC isozymes to the central nervous system development and aging, the expression of rat brain caspase family proteins in development and aging, and their subcellular distribution were also assessed using immunochemical detection.
|