title: Enhanced anandamide degradation is associated with neuronal apoptosis induced by the HIV-1 coat glycoprotein gp120 in the rat neocortex.
abstract: Human immunodeficiency virus type-1 coat glycoprotein gp120 causes delayed apoptosis in rat brain neocortex. Here, we investigated the possible role of the endocannabinoid system in this process. It is shown that gp120 causes a time-dependent increase in the activity and immunoreactivity of the anandamide (AEA)-hydrolyzing enzyme fatty acid amide hydrolase (FAAH), paralleled by increased activity of the AEA membrane transporter and decreased endogenous levels of AEA. The AEA-synthesizing phospholipase D and the AEA-binding receptors were not affected by gp120. None of the changes induced by gp120 in the cortex were induced by bovine serum albumin, nor were they observed in the hippocampus of the same animals. Also, the activity of 5-lipoxygenase, which generates AEA derivatives able to inhibit FAAH, decreased down to approximately 25% of the control activity upon gp120 treatment, due to reduced protein level ( approximately 45%). In addition, the FAAH inhibitor methyl-arachidonoyl fluorophosphonate significantly reduced gp120-induced apoptosis in rat brain neocortex, whereas selective blockers of AEA membrane transporter or of AEA-binding receptors were ineffective. Taken together, these results suggest that gp120, by activating FAAH, decreases endogenous levels of AEA, and the latter effect seems instrumental in the execution of delayed neuronal apoptosis in the brain neocortex of rats.
authors.affiliation: Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, I-64100 Teramo, Italy. Maccarrone@unite.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.forename: Silvia
authors.initials: S
authors.lastname: Piccirilli
authors.forename: Natalia
authors.initials: N
authors.lastname: Battista
authors.forename: Claudio
authors.initials: C
authors.lastname: Del Duca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: M Tiziana
authors.initials: MT
authors.lastname: Corasaniti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Finazzi-Agrò
authors.forename: Giacinto
authors.initials: G
authors.lastname: Bagetta
mesh_terms: D000581:Amidohydrolases / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000633:toxicity*; D007276:Injections, Intraventricular; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D063065:Organophosphonates / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001094:Arachidonate 5-Lipoxygenase; D001095:Arachidonic Acids; D002352:Carrier Proteins; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D015699:HIV Envelope Protein gp120; D063065:Organophosphonates; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C104810:methyl arachidonylfluorophosphonate; C078814:anandamide