| Project/Area Number |
62580213
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
分子遺伝学・分子生理学
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SHINGAI Ryuzo (1988) Assistant Yamaguchi University School of Medicine, 医学部, 助手 (00089088)
青島 均 (1987) 山口大学, 教養部, 助教授 (20089907)
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| Co-Investigator(Kenkyū-buntansha) |
BAN Takashi Professor Yamaguchi University School of Medicine, 医学部, 教授 (50101069)
新貝 鉚蔵 山口大学, 医学部, 助手 (00089088)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Lipid hydroperoxide / Zenopus oocytes / nRNA of rat brain / Acetylcholine receptor / Cultured neurons / アセチルコリン受容体 / 脱感作 / γ-アミノ酪酸受容体 |
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| Research Abstract |
The effect of 13-L-hydroperoxylinoleic acid(LOOH) on both Xenopus oocytes and neurotransmitter receptors synthesized in the oocytes was studied by electrophysiological and ion flux measurement. Addition of LOOH to the incubation mixture of the oocytes raised the membrane potential of the oocytes. Addition of LOOH caused an increase of Li^+ and ^<45>CA^<2+> uptake into the oocytes. However, production of alkoxy radicals by the addition of FeCl2 to the incubation mixture containing LOOH not accelerate the damage to the oocytes. So essential toxicity is caused possibly by an increase in the membrane permeability resulting from disturbance of the lipid bilayer arrangement, not from production of active alkoxy redicals during decomposition of LOOH. Nicotinic acetylcholine and -aminobutyric acid receptors acid receptors were synthsized in Xenopus oocytes by injecting mRNA p repared from Electrophorus electricus electroplax and rat brain. LOOH noncompetitively inhibited the function of these receptors and also increased the rate of desensitization of the receptors.
Ionic current induced by LOOH application was measured in cultured neurons from rat brain under the whole cell clamp condition. Power spectrum of the current fluctuation did not fit a sum of lorentzians suggesting that the increase in conductance by LOOH is not due to activation of ion channels. Effect of LOOH (1nM-100uM) added in culture medium for 3 or 7 days on the survival rate of neurons was studied for cultured neurons from corted, hippocampus and hypothalamus. The dose-survival rate curves were obtained by counting living neurons. At 100 m, almost all neurons died within 3 days. Decrease in the survival rate by LOOH was largest in hippocampal neurons. In cortical and hypothalamic neurons, the survival rate around at 10 nm was larger than that of the control without LOOH. We speculate that young healthy neurons can overcome damage by a very low concentration of LOOH.
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