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Increases in expression of 14‐3‐3 eta and 14‐3‐3 zeta transcripts during neuroprotection induced by Δ 9 ‐tetrahydrocannabinol in AF5 cells
Author(s) -
Chen Jia,
Lee ChunTing,
Errico Stacie L.,
Becker Kevin G.,
Freed William J.
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21304
Subject(s) - neuroprotection , nmda receptor , programmed cell death , microbiology and biotechnology , chemistry , pharmacology , biology , biochemistry , apoptosis , receptor
The molecular mechanisms involved in N‐methyl‐D‐aspartate (NMDA)‐induced cell death and Δ9‐tetrahydrocannabinol (THC)‐induced neuroprotection were investigated in vitro with an AF5 neural progenitor cell line model. By microarray analysis, Ywhah, CK1, Hsp60, Pdcd 4, and Pdcd 7 were identified as being strongly regulated by both NMDA toxicity and THC neuroprotection. The 14‐3‐3 eta (14‐3‐3η; gene symbol Ywhah) and 14‐3‐3 zeta (14‐3‐3ζ; gene symbol Ywhaz) transcripts were deceased by NMDA treatment and increased by THC treatment prior to NMDA, as measured by cDNA microarray analysis and quantitative real‐time RT‐PCR. Other 14‐3‐3 isoforms were unchanged. Whereas up‐regulation of 14‐3‐3ζ expression was observed 30 min after treatment with THC plus NMDA, down‐regulation by NMDA alone was not seen until 16 hr after treatment. By Western blotting, THC increased 14‐3‐3 protein only in cells that were also treated with NMDA. Overexpression of 14‐3‐3η or 14‐3‐3ζ by transient plasmid transfection increased 14‐3‐3 protein levels and decreased NMDA‐induced cell death. These data suggest that increases in 14‐3‐3 proteins mediate THC‐induced neuroprotection under conditions of NMDA‐induced cellular stress. © 2007 Wiley‐Liss, Inc.