Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells
6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson's disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2010/818497 |
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| author | Katarzyna Mnich David P. Finn Eilis Dowd Adrienne M. Gorman |
| author_facet | Katarzyna Mnich David P. Finn Eilis Dowd Adrienne M. Gorman |
| author_sort | Katarzyna Mnich |
| collection | DOAJ |
| description | 6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson's disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma PC12 cells. Morphological analysis and caspase-3 activity assay revealed that anandamide inhibited 6-OHDA-induced apoptosis. The protection was not affected by antagonists of either cannabinoid receptors (CB1 or CB2) or the vanilloid receptor TRPV1. Anandamide-dependent protection was reduced by pretreatment with LY294002 (inhibitor of phosphatidylinositol 3-kinase, PI3K) and unaffected by U0126 (inhibitor of extracellularly-regulated kinase). Interestingly, phosphorylation of c-Jun-NH2-terminal kinase (JNK) in cells exposed to 6-OHDA was strongly reduced by anandamide pre-treatment. Furthermore, 6-OHDA induced c-Jun activation and increased Bim expression, both of which were inhibited by anandamide. Together, these data demonstrate antiapoptotic effects of anandamide and also suggest a role for activation of PI3K and inhibition of JNK signalling in anandamide-mediated protection against 6-OHDA. |
| format | Article |
| id | doaj-art-ec1acc946a344650a164e4ffcb1591e5 |
| institution | OA Journals |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-ec1acc946a344650a164e4ffcb1591e52025-08-20T02:21:49ZengWileyInternational Journal of Cell Biology1687-88761687-88842010-01-01201010.1155/2010/818497818497Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 CellsKatarzyna Mnich0David P. Finn1Eilis Dowd2Adrienne M. Gorman3School of Natural Sciences, National University of Ireland, Galway, IrelandSchool of Medicine, National University of Ireland, Galway, IrelandSchool of Medicine, National University of Ireland, Galway, IrelandSchool of Natural Sciences, National University of Ireland, Galway, Ireland6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson's disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma PC12 cells. Morphological analysis and caspase-3 activity assay revealed that anandamide inhibited 6-OHDA-induced apoptosis. The protection was not affected by antagonists of either cannabinoid receptors (CB1 or CB2) or the vanilloid receptor TRPV1. Anandamide-dependent protection was reduced by pretreatment with LY294002 (inhibitor of phosphatidylinositol 3-kinase, PI3K) and unaffected by U0126 (inhibitor of extracellularly-regulated kinase). Interestingly, phosphorylation of c-Jun-NH2-terminal kinase (JNK) in cells exposed to 6-OHDA was strongly reduced by anandamide pre-treatment. Furthermore, 6-OHDA induced c-Jun activation and increased Bim expression, both of which were inhibited by anandamide. Together, these data demonstrate antiapoptotic effects of anandamide and also suggest a role for activation of PI3K and inhibition of JNK signalling in anandamide-mediated protection against 6-OHDA.http://dx.doi.org/10.1155/2010/818497 |
| spellingShingle | Katarzyna Mnich David P. Finn Eilis Dowd Adrienne M. Gorman Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells International Journal of Cell Biology |
| title | Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells |
| title_full | Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells |
| title_fullStr | Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells |
| title_full_unstemmed | Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells |
| title_short | Inhibition by Anandamide of 6-Hydroxydopamine-Induced Cell Death in PC12 Cells |
| title_sort | inhibition by anandamide of 6 hydroxydopamine induced cell death in pc12 cells |
| url | http://dx.doi.org/10.1155/2010/818497 |
| work_keys_str_mv | AT katarzynamnich inhibitionbyanandamideof6hydroxydopamineinducedcelldeathinpc12cells AT davidpfinn inhibitionbyanandamideof6hydroxydopamineinducedcelldeathinpc12cells AT eilisdowd inhibitionbyanandamideof6hydroxydopamineinducedcelldeathinpc12cells AT adriennemgorman inhibitionbyanandamideof6hydroxydopamineinducedcelldeathinpc12cells |