Neuroscience 2003 Abstract
| Presentation Number: | 147.6 |
|---|---|
| Abstract Title: | Involvement of raidd in trophic factor deprivation-induced neuronal death. |
| Authors: |
Wang, Q.*1
; Jabado, O.1
; Rideout, H. J.1
; Troy, C. M.1,2
; Greene, L. A.2
; Stefanis, L.1,2
1Neurol., Columbia Univ., New York, NY 2Pathology, Columbia Univ., New York, NY |
| Primary Theme and Topics |
Development - Trophic Factors and Developmental Cell Death -- Trophic factors and cell death |
| Session: |
147. Trophic Factors & Cell Death I Poster |
| Presentation Time: | Sunday, November 9, 2003 9:00 AM-10:00 AM |
| Location: | Morial Convention Center - Hall F-I, Board # C47 |
| Keywords: | PC12, APOPTOSIS, CASPASE, CELL DEATH |
We have previously reported that caspase 2 is essential for trophic factor deprivation-induced death of PC12 cells and sympathetic neurons (Troy et al., 1997), and that it is likely not processed by a caspase 3-like activity (Stefanis et al., 1998). The mechanisms of caspase 2 activation and its exact position within the death pathway in this model remain unclear. We have cloned by RACE the rat homologue of the caspase 2 adaptor RAIDD from PC12 cells (Yeasmin et al., SFN Abstracts 227.24, 2000). RAIDD is expressed in a predominantly cytoplasmic fashion in PC12 cells and neonatal rat sympathetic neurons. There are no observable changes in its expression or localization following trophic deprivation. Based on co-immunoprecipitation experiments however, RAIDD appears to associate with caspase 2 following serum deprivation from PC12 cells. To examine whether RAIDD is necessary for trophic deprivation-induced death, we have generated small interfering (si) RNAs directed against RAIDD. Two such siRNAs inhibit specifically the expression of rat, but not human, RAIDD that is overexpressed by transfection into PC12 cells and sympathetic neurons. These siRNAs, when compared to a control siRNA, provide partial protection against trophic deprivation-induced death of PC12 cells and sympathetic neurons. The relative magnitude of the protection afforded by the two siRNAs is related to the extent that they inhibit the expression of RAIDD. Expression of the RAIDD siRNAs also leads to a reduction of caspase 3 activation in serum-deprived PC12 cells. These results suggest that RAIDD is involved in trophic deprivation-induced neuronal death, likely through its interaction with caspase 2, and that its site of action lies upstream of caspase 3 activation.
Supported by March of Dimes Grant 1-FY99-318, NINDS, MDA
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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