2001 Fiscal Year Final Research Report Summary
INVESTIGATION OF DIFFERENTIAL SUSCEPTIBILITY TO CELL DEATH IN POLYGLUTAMINE DISEASES
| Project/Area Number |
12670591
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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 |
Neurology
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| Research Institution | UNIVERSITY OF TSUKUBA |
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Principal Investigator |
YOSHIZAWA Toshihiro DEPARTMENT OF NEUROLOGY, INSTITUTE OF CLINICAL MEDICINE, UNIVERSITY OF TSUKUBA, ASSISTANT PROFESSOR, 臨床医学系, 講師 (50212311)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Machado-Joseph disease / polyglutamine / ataxin-3 / cell death / aggregation / polyclonal antibody / neuron |
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| Research Abstract |
To investigate the mechanisms of selective neuronal loss observed in the polyglutamine disease, we used Machado-Joseph disease (MJD) as a model for polyglutamine diseases. (1) We developed the polyclonal antibody raised against N-terminal side of ataxin-3 and immunohistochemically examined MJD brain with this antibody. In the MJD potine nucleus, soma of neurons and intranuclear inclusions were positively stained with anti-N-terminal ataxin-3 antibody, suggesting that intranuclear inclusions contain the epitope of N-terminal portion of ataxin-3. (2) Next, we investigate the aggregate formation and cytotoxicity produced by N-terminal truncated ataxin-3 (Q77) in different cultured cells (HeLa, Swiss3T3, P19, C2C12, COS-1, BHK-21, PC12, Neuro2a). Frequency of aggregates and cell death varies among different cell lines. Aggregate frequency was not correlated with that of cell death. Our results demonstrated that the differential susceptibility to death in various cell lines was evident even in the expression of N-terminal truncated ataxin-3 (Q77), suggesting that we do not need to hypothesize the presence of processing enzyme of ataxin-3 to explain the differential susceptibility.
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Research Products
(10 results)
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[Publications] Hatakeyama S, Wakamori M, Ino M, Miyamoto N, Takahashi E, Yoshinaga T, Sawada K, Imoto K, Tanaka I, Yoshizawa T, Nishizawa Y, Mori Y, Niidome T, Shoji S: "Differential nociceptive responses in mice lacking the alpha 1B subunit of N-type Ca2+ channels"Neuroreport. 118. 2423-2427 (2001)
Description
「研究成果報告書概要(欧文)」より
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