1995 Fiscal Year Final Research Report Summary
Studies on Regulatory Mechanisms of Developmental Neuronal Cell Death
| Project/Area Number |
06454686
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Developmental biology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KOIKE Tatsuro Hokkaido Univ.Grad.Sch.of Sci.Professor, 大学院理学研究科, 教授 (80128131)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Apoptosis / Programd cell death / Calcium / ER / Molecular chaperone / Chromatin condeusation / c-fos / Superior servical gauglion |
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| Research Abstract |
We have shown previously that neuronal survival under depolarizing conditions correlates well with sustained levels of cytoplasmic free calcium ([Ca^<2+>]_i) in rat superior cervical ganglion (SCG) cells and cerebellar granule neurons. Moreover, developmental acquisition of trophic factor-independent survival is coincident with a gradual elevation of[Ca^<2+>]_i in SCG and sensory neurons. In contrast, when basal levels of[Ca^<2+>]_i in these neurons were decreased by treatment with an excessive dose of the Ca^<2+> chelator BAPATAAM,these neurons died following fragmentation of chromatin as visualized by fluorescent staining with bis-benzamide, a hallmark of apoptosis. Indeed, our Ca^<2+> set-point hypothesis predicts that a decrease in the level of cytoplasmic Ca^<2+> occurs during neuronal death following trophic factor withdrawal. In support of this, when SCG neurons were treated with 10-20 muM BAPTA-AM thus chelating the level of intracellular Ca^<2+>, they became resistant to NGF deprivation. Fura-2 measurements of[Ca^<2+>]_i also indicated a decrease in basal Ca^<2+> levels. Since there is evidence suggesting that NGF facilitates Ca^<2+>-dependent processes in these neurons, NGF deprivation causes a disruption of Ca^<2+> homeostasis in these neurons thus leading to the activation of neuronal apoptosis cascades.
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Research Products
(14 results)
