2001 Fiscal Year Final Research Report Summary
Studies on mechanism of neuronal death induced by an amyotrophic lateral sclerosis
| Project/Area Number |
12672227
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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 |
応用薬理学・医療系薬学
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| Research Institution | Nihon University |
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Principal Investigator |
ITO Yoshihisa Nihon University, College of Pharmacy, associate professor, 薬学部, 助教授 (50151551)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGE Kumiko Nihon University, College of Pharmacy, Full-time lecturer, 薬学部, 講師 (40212873)
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| Project Period (FY) |
2000 – 2001
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| Keywords | 4-hydroxynonenal / amyloid β-protein / neuronal death / cultured neurons / hippocampus / spinal cord / s-allyl-L-cysteine |
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| Research Abstract |
S-allyl-L-cysteine (SAC), one of the organosulfur compounds in aged garlic extract, has been shown to possess various biological effects including neurotrophic activity. We characterized neuronal death induced by amyloid beta-protein (Aβ), 4-hydroxynonenal (HNE), Tunicamycin (Tm) and trophic factor deprivation, and investigated whether and how SAC could prevent these neuronal deaths in cultured hippocampal neurons in rats. Treatment with SAC protected against A- and tunicamycin-induced neuronal death which has been shown to be mediated predominantly through the down regulation of endoplasmic reticurum (ER) stress (ER) response in a concentration-dependent manner. In contrast, it afforded no protection against HNE- and trophic factor deprivation-induced cell death, in which caspase-3 played a pivotal role in these neuronal deaths. These results suggest that SAC could protect against neuronal cell death which is triggered by ER dysfunction in the hippocampus, and that it has no effect on neuronal death which is dependent on caspase-3 mediated pathway. We also examined HNE-induced neurotoxicity in the absence and presence of L-glutamic acid (Glu) in organotypic hippocampal and spinal cord slice coltures prepared from 6- or 7-day-old rats. In slice cultures, little neurotoxicity was observed by the treatment with HNE (25-100 μM) or Aβ (25 and 50 mM) alone. Although Glu (2.5 and 5.0 mM) alone exhibited slight neuronal death in cultured spinal cord, this neuronal death was dramatically increased in the presence of HNE (50 μM). A pan-caspase inhibitor, z-VAD-fmk, partially protected neurons from neuronal death induced by Glu in combination with HNE. These results suggest that caspases-mediated pathway is, at lease in part, responsible for this neuronal death.
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Research Products
(4 results)
