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Secretory phospholipase A(2) induces delayed neuronal COX-2 expression compared with glutamate
Miriam Kolko1, Marianne Nielsen, Nicolas G Bazan
1Laboratory of Neuropathology, University of Copenhagen, Copenhagen, Denmark.
Journal of Neuroscience Research
|July 12, 2002
Summary
Secretory phospholipase A(2) (sPLA(2)) selectively induces cyclooxygenase-2 (COX-2) in neurons. This induction is delayed compared to glutamate, suggesting distinct signaling pathways involved in brain responses.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Secretory phospholipase A(2) (sPLA(2)) agonists enhance glutamate-induced neuronal death.
- The role of cyclooxygenase-2 (COX-2) in the brain's response to sPLA(2) is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that COX-2 expression is involved in the brain's response to sPLA(2).
- To compare the signaling pathways of sPLA(2)-induced and glutamate-induced COX-2 expression.
Main Methods:
- In situ hybridization using radiolabeled probes and immunohistochemistry were used to monitor gene expression in rat striatum after sPLA(2) injection.
- Early-response genes (COX-2, c-fos, c-jun, COX-1) were analyzed at different time points post-injection.
Main Results:
- sPLA(2) selectively induced neuronal COX-2, c-fos, and c-jun, but not COX-1.
- COX-2 induction by sPLA(2) was observed at 4-8 hours post-injection, while glutamate induced early-response genes at 2 hours.
- c-fos and c-jun were induced early (2 hours) around the infarct area, with a time course similar to COX-2.
Conclusions:
- sPLA(2) selectively induces neuronal COX-2 expression.
- The mechanisms underlying sPLA(2)-induced COX-2 expression differ from those of glutamate-induced COX-2 expression.
- sPLA(2) may modulate neuronal COX-2 expression through distinct signaling pathways.