Neuroscience 2003 Abstract
| Presentation Number: | 216.15 |
|---|---|
| Abstract Title: | HIV/gp120 induced neuronal apoptosis involves p53 mediated trans-repression of XIAP. |
| Authors: |
Tun, C.*1
; Guo, W.1
; Libby, R.3
; Garden, G. A.1
; Morrison, R. S.2
1Neurol., Univ. of Washington, Seattle, WA 2Neurological Surgery, Univ. of Washington, Seattle, WA 3Lab. Med., Univ. of Washington, Seattle, WA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neuroimmunology and Infections |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Neurodegenerative Disorders<br />-- Other |
| Session: |
216. Neuroimmunology and Infections: HIV & the CNS Poster |
| Presentation Time: | Sunday, November 9, 2003 10:00 AM-11:00 AM |
| Location: | Morial Convention Center - Hall F-I, Board # VV18 |
| Keywords: | caspase-3, TISSUE CULTURE, INHIBITION |
The p53 tumor suppressor protein plays a key role in regulating cell cycle progression and apoptosis. Neuronal apoptosis resulting from DNA damage, hypoxia, and oxidative injury is mediated by p53. Using mixed cerebrocortical cultures from wild type (p53+/+) and p53 null (p53-/-) mice, we have now shown that neuronal apoptosis induced by the HIV coat protein gp120 also requires p53 (see Guo et al., 2003 SFN abstract). In contrast to p53+/+ cultures, HIV/gp120 does not induces caspase-3 enzymatic activity in p53-/- cultures, as measured by a fluorogenic substrate cleavage assay. Furthermore, caspase-3 cleavage products visualized by immunoreactivity for caspase-3-cleaved amyloid precursor protein, did not accumulate in neurons from p53-/- mice. Despite these findings, neurons and microglia from both genotypes develop increased immunoreactivity for activated caspase-3 after gp120 exposure. These findings suggest that in this system, p53 propagates its apoptotic action downstream of caspase-3 activation, perhaps through modulation of an endogenous caspase inhibitor. The X-linked inhibitor of apoptosis protein (XIAP) is a member a family of proteins that contain multiple 70 amino acid repeats termed baculoviral IAP repeats (BIR’s). These BIR repeats are direct inhibitors of caspase-3 and -7. Mixed cerebrocortical culture lysates from p53-/- mice contain significantly more XIAP protein than lysates from cultures. When p53 expression was reconstituted in p53-/- cerebrocortical cultures by infection with a human p53 expressing adenovirus, XIAP protein content was diminished to near the level observed in p53+/+ cultures. Taken together, these data suggest that p53 promotes gp120 induced neuronal apoptosis in part through transrepression of caspase inhibitors, including XIAP.
Supported by NIH grants K08 NS02063 and RO1 NS35533
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
Copyright © 2003-2026 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
