Neuroscience 2005 Abstract
| Presentation Number: | 639.10 |
|---|---|
| Abstract Title: | Glucocorticoids exacerbate hypoxia induced Bnip3 mRNA expression to increase cell death in primary cortical neurons. |
| Authors: |
Sandau, U. S.*1
; Handa, R. J.1
1Biomedical Sciences, Colorado State Univ., Fort Collins, CO |
| Primary Theme and Topics |
Homeostatic and Neuroendocrine Systems - Stress and the Brain -- Cellular actions of stress |
| Session: |
639. Cellular Actions of Stress: Neuromodulators Poster |
| Presentation Time: | Tuesday, November 15, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # DD21 |
| Keywords: | glucocorticoid, apoptosis, hypoxia, Bcl-2 |
In many cell types, hypoxia upregulates the expression of the pro-apoptotic gene Bnip3 which results in cell death. Bnip3 mRNA is also increased by RU28362, a glucocorticoid receptor specific agonist, and this correlates with augmented cell death in primary cortical neurons (Sandau and Handa, SFN. Abst. 837.21, 2004). In this study, we further examined Bnip3 mRNA regulation in primary cortical neurons by hypoxic insult in conjunction with glucocorticoid treatment. Additionally, we determined if increases in Bnip3 mRNA correlated with increases in cell death. Cortical neurons were harvested from embryonic day 18 rat fetuses. Neurons were treated with 1 of 3 doses of RU28362 (0.1, 1.0, or 10.0nM) or vehicle and maintained in normoxic (20% O2) or hypoxic (1% O2) conditions for 72 hours. Bnip3 mRNA expression was assayed by quantitative real time RT-PCR. Hypoxia caused a 0.5 fold increase in Bnip3 mRNA levels compared to vehicle treated normoxic cells. However, cells treated with RU28362 in conjunction with hypoxia showed a 4 fold exacerbation of Bnip3 mRNA expression (p<0.001) in comparison to vehicle treated normoxic cells. Whether increases in Bnip3 actually mediate cortical neuron cell death was addressed by transfecting primary neurons with Bnip3 or Bnip3-TM containing plasmid vectors. Bnip3-TM has a deletion of the Bnip3 transmembrane domain region which is required for the apoptotic actions of Bnip3. Cell death was assayed in transfected neurons by quantifying viable cells. Transfection of the Bnip3 plasmid increased cell death by 17% (p<0.05) compared to control neurons transfected with empty plasmid. Transfection of Bnip3-TM had no effect. These data show that hypoxia mediated upregulation of Bnip3 mRNA levels is exacerbated by glucocorticoids. Furthermore, increases in Bnip3 expression in cortical neurons induces cell death. Thus increases in neuronal death may underlie neuropathologies associated with glucocorticoid treatment during hypoxic insults.
Supported by NIH (F31 NS046959 and RO1 NS039951)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
Copyright © 2005-2026 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.
