Neuroscience 2004 Abstract
| Presentation Number: | 728.12 |
|---|---|
| Abstract Title: | Involvement of 14-3-3 proteins and the p38 MAPK signaling pathway in the neuroprotective effect of delta9-tetrahydrocannabinol in AF5 cells. |
| Authors: |
Chen, J.*1
; Errico, S.1
; Becker, K. G.2
; Freed, W. J.1
1Cell. Neurobiology Res. Br., IRP/NIDA/NIH/DHHS, Baltimore, MD 2MD, 5500 Nathan Shock Dr, 21224, |
| Primary Theme and Topics |
Development - Trophic Factors and Developmental Cell Death -- Neurotrophins: receptors and signaling mechanisms |
| Session: |
728. Trophic Factors and Cell Death III Poster |
| Presentation Time: | Tuesday, October 26, 2004 4:00 PM-5:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # F28 |
| Keywords: | NEUROTOXICITY, CANNABINOIDS, NEUROPROTECTION, SIGNAL TRANSDUCTION |
In previous studies, we found that THC and capsaicin can protect AF5 cells from NMDA-induced cell toxicity, an effect apparently related to antioxidant properties of these compounds (Chen J, et al., in preparation). We have investigated the signaling pathways involved in neuroprotection against NMDA-induced toxicity mediated by THC and capsaicin in AF5 cells. Gene expression profiles were studied using a mouse developmental cDNA microarray. Expression of the 14-3-3 transcript was altered after exposure to NMDA alone, NMDA plus cannabinoids, or capsaicin. The 14-3-3 transcript was decreased by 2.14-fold after exposure to 7.5 mM NMDA as compared to the untreated control condition, while THC increased 14-3-3 expression by 3.08 fold as compared to NMDA alone. Capsaicin also significantly increased the 14-3-3 transcript, but to a smaller degree than THC. WIN55,212 produced no significant change. Changes in 14-3-3 expression measured by Q-PCR were consistent with those obtained using microarrays. The 14-3-3 protein was detectable in AF5 cells by Western blotting (30KDa), and 14-3-3 was increased significantly 16h following exposure to THC plus NMDA, as compared to NMDA alone. Increased phosphorylated p38 MAPK was also detected after NMDA treatment; however, activation of phosphorylated p38 MAPK was blocked by pretreatment with THC prior to NMDA. These data indicate that the 14-3-3 protein and the p38 MAPK pathway are involved in the cell death induced by NMDA, and upregulation of 14-3-3 may mediate the effect of THC in blocking apoptosis. Therefore, 14-3-3 proteins may respond to putative non-CB1 antioxidant-mediated neuroprotective effects of THC and capsaicin.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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