Cannabinoid Receptor Agonist WIN-55,212-2 Protects Differentiated PC12 Cells From Organophosphorus- Induced Apoptosis

Sadri, Soheil; Bahrami, Fatemeh; Khazaei, Mozafar; Hashemi, Masih; Asgari, Asghar

doi:10.1177/1091581809359708

Cited by 14 publications

(6 citation statements)

References 40 publications

(55 reference statements)

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“…The role of direct ACEA-dependent CB1 receptor activation in neuroprotection is confirmed by our finding that CB1 receptor antagonist AM251 significantly decreased cell viability and CB1 receptor expression induced by ACEA in PC12 cells treated with POX. Consistent with these results are our previous studies which have shown that cannabinoid receptor agonist WIN-55,212-2 protects differentiated PC12 cells from organophosphorus-induced apoptosis [43] and that stimulation of CB1 cannabinoid and NMDA receptors increases neuroprotective effect against diazinon-induced neurotoxicity [44].…”

Section: Resultssupporting

confidence: 90%

Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells

Salem¹,

Bahrami²,

Bahari³

et al. 2019

Ukr.Biochem.J.

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Pharmacological studies allow to suggest that activation of cannabinoid type 1 receptors (CB1) have a neuroprotective role against toxicity induced by organophosphate agents, but the exact mechanisms of this effect as well as interaction with receptors of other types are far from clear. Therefore, the aim of current study was to evaluate the effect of CB1 and NMDA receptors agonists on cell viability and biomarkers of oxidative stress and lipid peroxidation in PC12 cells exposed to paraoxon. PC12 cells were exposed to 100 µm paraoxon as organophosphate agent. Treatments with 1 µm arachidonyl-2'-chloroethylamide (aCea) as specific agonist of CB1 receptors, 100 µM N-methyl-D-aspartate (NMDA) as agonist of NMDA receptors and 1 µm am251 as antagonist of CB1 receptors were done. Cell via bility and biomarkers of oxidative stress were evaluated after 48 h of incubation. The level of CB1 receptor protein was evaluated by Western blotting. It was demonstrated that PC12 cells treatment with paraoxon led to cell viability inhibition, glutathione level, superoxide dismutase and catalase activity reduction, lipid peroxidation intensification and CB1 receptor expression attenuation. application of aCea and Nmda was shown to be followed by normalization of these indices. The protective effect of ACEA was abolished when the CB1 receptors antagonist AM251 was applied. The study revealed that application of aCea and Nmda can protect PC12 cells against paraoxon induced toxicity through antioxidant capacity increment, lipid peroxidation inhibition and enhanced expression of CB1 receptors. K e y w o r d s: CB1 receptors, cannabinoid, paraoxon , PC12 cells, oxidative stress.

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Section: Resultssupporting

confidence: 90%

Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells

Salem¹,

Bahrami²,

Bahari³

et al. 2019

Ukr.Biochem.J.

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“…Diazinon in the 200 µM dose decreased cell survival and CB1 receptor expression after 48 h-long exposure. In our earlier works with OPs, we found that sublethal concentrations of diazinon inhibited the outgrowth of axon-like processes and induced apoptosis of differentiated PC12 cells [4,18]. Other researchers also reported that diazoxon inhibited AChE activity and reduced transcripts of the α4 and β2 subunits of nAChRs (at the mRNA level) in PC12 cells [2].…”

Section: Discussionmentioning

confidence: 59%

“…AM251 did not decrease the viability and CB1 receptor expression increased by WIN55,212-2 in PC12 cells. However, in our previous work where PC12 cells were differentiated under the action of neural growth factor (NGF), AM251 inhibited the neuroprotective effect of WIN55,212-2 [4]. Hence, the reason for this disparity seems to be related to the cell differentiation process.…”

Section: Discussionmentioning

confidence: 92%

“…Different studies showed that diazinon inhibits acetylcholinesterase (AChE) activity and protein synthesis in PC12 cells [2]. In other studies, it was reported that this compound disturbs DNA synthesis in and induces apoptosis of PC12 cells [3,4]. Sublethal concentrations of diazinon inhibit the outgrowth of axon-like processes from differentiating mouse N2a neuroblastoma and PC12 cells [4,5].…”

Section: Diazinonmentioning

confidence: 99%

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Stimulation of CB1 Cannabinoid and NMDA Receptors Increases Neuroprotective Effect against Diazinon-Induced Neurotoxicity

et al. 2013

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Cannabinoids have been shown to exert a neuroprotective influence in organophosphorusinduced toxicity. In our study, we examined the effects of the cannabinoid receptor agonist WIN55,212-2 and NMDA receptor agonist NMDA on cell death in the pheochromocytoma cell line PC12 subjected to the action of an organophosphorus compound, diazinon. Diazinon decreased cell viability in a concentration-dependent manner. Following the exposure of PC12 cells to 200 µM diazinon for 48 h, reductions in cell survival and protein level of CB1 receptors were observed. Treatment of the cells with 0.1 µM WIN55,212-2 and 100 µM NMDA prior to diazinon exposure significantly elevated the cell survival level and protein level of CB1 receptors. The cannabinoid antagonist AM251 (1 µM) did not inhibit the neuroprotection effect induced by WIN55,212-2, indicating that the neuroprotective effect of this agonist was cannabinoid receptor-independent. The NMDA receptor antagonist MK-801 (1 µM) enhanced diazinon-mediated neurotoxicity suggesting that precisely NMDA receptors may play a protective role.

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“…These studies point in different directions showing both pro and antiapoptotic effects, depending on experimental system, cannabinoid type and dose. A recent study using R(+)WIN55,212-2, however, found that this cannabinoid inhibits apoptosis in PC12 cells (Sadri, Bahrami, Khazaei, Hashemi, & Asgari, 2010).…”

Section: Introductionmentioning

confidence: 98%

Cannabinoid Treatment Renders Neurons Less Vulnerable Than Oligodendrocytes in Experimental Autoimmune Encephalomyelitis

Hasseldam

2011

International Journal of Neuroscience

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Using the rat model Experimental Autoimmune Encephalomyelitis (EAE), we have investigated the cytokinetical and cellular events of axonal degeneration and demyelination following treatment with 5 mg/kg/24h R(+)WIN55,212-2 or 10 mg/kg/24h R(+)WIN55,212-2, which have immunosuppressive effects. EAE was induced using MOG(1-125) in Dark Agouti rats and treatment was initiated at symptom debut and continued until first relapse culminated. The central nervous system (CNS) cell death including caspase and calpain activation, axonal degeneration and demyelination as well as a wide range of immunological parameters were quantified. We found a significant reduction in axonal degeneration associated with reduced calpain 1 following treatment with 5 mg/kg/24h R(+)WIN55,212-2. Treatment with 10 mg/kg/24h resulted furthermore in an improved clinical performance and a reduction in inflammatory activity and demyelination. Furthermore, the cytokines IL-2, IL-6, IL-10, RANTES, and TGF-β were significantly reduced as were the cellular infiltration with regulatory T cells. We suggest that cannabinoids in low doses are neuroprotective through a reduction in calpain 1 expression. Our study implies that long-term low-dose cannabinoid administration to multiple sclerosis (MS) patients could result in some degree of neuroprotection, and thereby slow down the atrophy associated with this disease.

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Cannabinoid Receptor Agonist WIN-55,212-2 Protects Differentiated PC12 Cells From Organophosphorus- Induced Apoptosis

Cited by 14 publications

References 40 publications

Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells

Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells

Stimulation of CB1 Cannabinoid and NMDA Receptors Increases Neuroprotective Effect against Diazinon-Induced Neurotoxicity

Cannabinoid Treatment Renders Neurons Less Vulnerable Than Oligodendrocytes in Experimental Autoimmune Encephalomyelitis

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