| Project/Area Number |
07660145
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bioproduction chemistry/Bioorganic chemistry
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| Research Institution | KONAN WOMEN'S JUNIOR COLLEGE |
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Principal Investigator |
TAKAHASHI Tsutomu KONAN WOMEN'S JUNIOR COLLEGE,Food and Nutrition, Professor, 生活科学科, 教授 (20099485)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Cytotoxicity / salsolinol / N-methyl-(R)-salsolinol / 1,2-Dimethyl-6,7-dihydroxyisoquinolinium ion / neuroblastoma SH-SY5Y cells / Parkinson's disease / beta-cyclodextrin / HPLC / 光学異性体 / イソキノリン類 / SH-SY5Y細胞 / ドパミン / イソキノリン / 複素環式アミン / パーキンソン病 / チロシン水酸化酵素 |
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| Research Abstract |
(1) A chromatographic procedure was divised for the quantitative determination of the enantiomers of salsolinol and N-methylsalsolinol, biologically important alkaloids. The enantiomers of salsolinol and N-methylsalsolinol were completely separated using a beta-cyclodextrin bonded column or beta-cyclodextrin as an addict in the mobile phase. The HPLC method was sensitive enough to detect the isoquinolines at the concentration less tha 0.1 pmol per injection. The presence of (R) -and (S) -salsolinol was confirmed in fermented foods and beverages, while N-methylsalsolinol was not detected.
(2) To assert the cytotoxicity quantitatively, a new assay method was devised. Endogenous catechol isoquinolines were examined for the cytotoxicity to human dopaminergic neuroblastoma SH-SY5Y cells, using Alamar Blue assay, an in situ calorimetric measurement of the reduction-oxidation potency. 1,2-Dimethyl-6,7-dihydroxyisoquinolinium ion [1,2-DMDHIQ+] was found to be the most potent toxin, and catechol isoquinolines were more toxic than isoquinolines without catechol structure. The results are discussed in relation to the mechanism underlying selective neurotoxicity of endogenous depaminergic neurotoxins.
(3)Dopamine-derived salsolinol and related compounds were examined for their selective neurotoxicity to dopamine neurons by injection into the rat striatum. Among salsolinol analogs examined, only N-methyl-(R)-salsolinol induced behavioral changes very similar to those in Parkinson's disease : hypokinesia.stiff tail, limb twitching at rest and postural abnormality.
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