Neuroscience 2002 Abstract
| Presentation Number: | 293.19 |
|---|---|
| Abstract Title: | Roles of p53 in Huntington's Disease: possible involvement in mitochondrial function and calcium homeostasis. |
| Authors: |
Bae, B. I.*1
; Igarashi, S.1,2
; Fujimuro, M.4
; Taya, Y.5
; Ozeki, Y.1,2
; Ross, C. A.1,2
; Snyder, S. H.1,2,3
; Sawa, A.1,2
1Neuroscience, Johns Hopkins Univ Sch Med, Baltimore, MD 2Psychiatry and Behavioral Sciences, Johns Hopkins Univ Sch Med, Baltimore, MD 3Pharmacology and Molecular Sciences, Johns Hopkins Univ Sch Med, Baltimore, MD 4Oncology, Johns Hopkins Univ Sch Med, Baltimore, MD 5National Cancer Center, Tokyo, Japan |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- Trinucleotide Repeat Diseases: Huntingtons Disease |
| Session: |
293. Neurodegenerative disorders: trinucleotide repeat diseases--Huntington's disease III Poster |
| Presentation Time: | Monday, November 4, 2002 10:00 AM-11:00 AM |
| Location: | Hall A2-B3 U-22 |
| Keywords: | Huntington's Disease, p53, mitochondria, calcium |
We have previously reported that p53 is highly upregulated by mutant Huntingtin (Htt) containing expanded polyglutamine repeats both in a HD cell model (PC12 cells with Htt) and Htt transgenic animals, which conferrs increased p53-mediated gene expression. We also reported that deletion of p53 increases cellular viability in HD cell model as well as normalized impaired behavior during rotarod tasks and reduced hyperactivity in rotational movements which are found in HD animal models (Bae et al, 2001, SFN Abstract). Here we present additional data to support roles of p53 in HD animal models: a reduced mortality and restoration of impaired pre-pulse inhibition in mutant Htt transgenic mice upon partial deletion of p53. Based on our previous finding that HD patient lymphoblasts display vulnerability in mitochondrial depolarization (Sawa et al,1999, Nat. Med.), we have analyzed mitochondrial membrane potential as an underling mechanism. We observed mitochondrial depolarization in PC12 cells expressing mutant Htt, but not normal Htt, prior to cell death. The mitochondrial depolarization was attenuated by the addition of a p53 inhibitor. Since mitochondria play a role in calcium homeostasis as well as cell death initiation, we are now studying intracellular calcium level of mutant Htt cells and their response to glutamate, with or without inhibition of p53.
Supported by PHS grant DA00266 and HDSA grant
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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