Anandamide protects from low serum-induced apoptosis via its degradation to ethanolamine.
Anandamide (AEA) is a lipid molecule belonging to the family of endocannabinoids. Various studies report neuroprotective activity of AEA against toxic insults, such as ischemic conditions and excitotoxicity, whereas some show that AEA has pro-apoptotic effects. Here we have shown that AEA confers a protective activity in N18TG2 murine neuroblastoma cells subjected to low serum-induced apoptosis. We have demonstrated that the protection from apoptosis by AEA is not mediated via the CB1 receptor, the CB2 receptor, or the vanilloid receptor 1. Interestingly, breakdown of AEA by fatty acid amide hydrolase is required for the protective effect of AEA. Furthermore, the ethanolamine (EA) generated in this reaction is the metabolite responsible for the protective response. The elevation in the levels of reactive oxygen species during low serum-induced apoptosis is not affected by AEA or EA. On the other hand, AEA and EA reduce caspase 3/7 activity, and AEA attenuates the cleavage of PARP-1. Taken together, our results demonstrate a role for AEA and EA in the protection against low serum-induced apoptosis.
Matas
Devorah
D
Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Juknat
Ana
A
Pietr
Maciej
M
Klin
Yael
Y
Vogel
Zvi
Z
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001095:Arachidonic Acids / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D019856:Ethanolamine / Q000378:metabolism*; D005434:Flow Cytometry; D007511:Ischemia; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D043882:Receptors, Cannabinoid / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D053148:Caspase 3; D053179:Caspase 7; D063388:Endocannabinoids; D019856:Ethanolamine; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; D043882:Receptors, Cannabinoid; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide