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    Article: The neuroprotective of cannabinoid receptor agonist (WIN55,212-2) in paraoxoninduced neurotoxicity in PC12 cells and N-methyl-D-aspartate receptor interaction
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    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 μM) in the presence or absence of WIN55,212-2 (0.1 μM), NMDA receptor agonist NMDA (100 μM), cannabinoid receptor antagonist AM251 and NMDA receptor antagonist MK801 (1 μM) 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 μM), 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 μM) prior to paraoxon exposure significantly elevated cell survival and protein level of the CB1 receptor (p<0.01). Also, AM251 (1μM) 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 μM) 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.
    Yakhteh Medical Journal. 01/2010; 12:183-190.
  • Article: Cannabinoid receptor agonist WIN-55,212-2 protects differentiated PC12 cells from organophosphorus- induced apoptosis.
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    ABSTRACT: Cannabinoid neuroprotection is usually greater in vivo than in neuronal cell culture systems. To the authors' knowledge, a good in vitro culture model for the neuroprotective effects of cannabinoids does not exist. Therefore, a 3-dimensional (3D) culture system was developed to investigate the neuroprotective effects of the cannabinoid receptor agonist WIN-55,212-2 on apoptosis of differentiated PC12 cells, caused by the organophosphorus compounds paraoxon and diazinon. Cells pretreated with WIN-55,212-2 were exposed to a proapoptotic concentration of paraoxon and diazinon. TUNEL was used to detect apoptosis, and neurite length was assessed by morphometry. Both paraoxon and diazinon induced apoptosis, although the latter was more potent. WIN-55,212-2 also protected cells from neurite retraction and DNA fragmentation induced by the OPs. The results suggest that WIN-55,212-2 protects PC12 cells cultured under 3D conditions from organophosphorus-induced apoptosis. This 3D culture system may prove to be a useful tool for investigating the neuroprotective effects of cannabinoids.
    International Journal of Toxicology 29(2):201-8. · 1.28 Impact Factor

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