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LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
Reactive oxygen species and p38 phosphorylation regulate the protective effect of Delta9-tetrahydrocannabinol in the
Jia Chen1, Stacie L Errico, William J Freed
1Development and Plasticity Section, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. jchen@intra.nida.nih.gov
Abstract:
NMDA causes oxidative stress in neurons, and produces cell death involving elements of both necrosis and apoptosis. To examine the neuroprotective mechanism of Delta9-tetrahydrocannabinol (THC) in NMDA-induced death of AF5 cells, we measured reactive oxygen species (ROS) formation after exposure to NMDA. ROS generation was increased by NMDA, and NMDA-induced ROS generation was significantly decreased by THC. Western blotting revealed an increase in phosphorylated p38 MAPK after NMDA treatment, which was also blocked by pretreatment with THC. The time course of ROS generation and activation of MAPK signaling pathways were similar. SB203580, a p38 inhibitor, partially blocked glutamate excitotoxicity in AF5 cells. The present data suggest that THC protects against NMDA-induced apoptosis in AF5 cells by blocking ROS generation and inhibiting the activation of p38-MAPK.
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