THE NEUROPROTECTIVE EFFECT OF CANNABINOID RECEPTOR AGONIST (WIN55,212-2) IN PARAOXON INDUCED NEUROTOXICITY IN PC12 CELLS AND N-METHYL-D-ASPARTATE RECEPTOR INTERACTION

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HASHEMI MANSOUREH; BAHRAMI FARIDEH; SAHRAEI HEDAYAT; GOLMANESH L.; SADRI SOHEYL

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Journal: Cell Journal (Yakhteh) Year:2010 | Volume:12 | Issue:2 (46) Page(s): 183-190

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Title

THE NEUROPROTECTIVE EFFECT OF CANNABINOID RECEPTOR AGONIST (WIN55,212-2) IN PARAOXON INDUCED NEUROTOXICITY IN PC12 CELLS AND N-METHYL-D-ASPARTATE RECEPTOR INTERACTION

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Keywords

WIN55Q1

212-2Q1

PARAOXONQ1

NMDAQ1

VIABILITYQ1

PC12 CELLSQ1

Abstract

Objective: Considering that cannabinoids protect neurons against neurodegeneration, in this study, the neuroprotective effect of WIN55,212-2 in PARAOXON induced neurotoxicity in PC12 CELLS and the role of the N-methyl-D-aspartate (NMDA) receptor were evaluated.Materials and Methods: In this study PC12 CELLS were maintained in Dulbecco's modified eagle’s medium (DMEM+F12) culture medium supplemented with 10% fetal bovine serum. The cells were treated with PARAOXON (200 mM) in the presence or absence of WIN55,212-2 (0.1 mM), NMDA receptor agonist NMDA (100 mM), cannabinoid receptor antagonist AM251 and NMDA receptor antagonist MK801 (1 mM) at 15 minutes intervals. After 48 hours of exposure, cellular VIABILITY and protein expression of the CB1 receptor were evaluated in PC12 CELLS. Results: Following the exposure of PC12 CELLS to PARAOXON (200 mM), a reduction in cell survival and protein level of the CB1 receptor was observed (p<0.01). Treatment of the cells with WIN55,212-2 (0.1 µM) and NMDA (100 mM) prior to PARAOXON exposure significantly elevated cell survival and protein level of the CB1 receptor (p<0.01). Also, AM251 (1mM) did not inhibit the cell survival and protein level of the CB1 receptor increase induced by WIN55,212-2 (p<0.001). However, MK801 (1 mM) did inhibit cell survival and protein expression of the CB1 receptor increase induced by NMDA (p<0.001).Conclusion: The results indicate that WIN55,212-2 and NMDA protect PC12 CELLS against PARAOXON induced toxicity. In addition, the neuroprotective effect of WIN55,212-2 and NMDA was cannabinoid receptor-independent and NMDA receptor dependent, respectively.

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