Enhanced anandamide degradation is associated with neuronal apoptosis induced by the HIV-1 coat glycoprotein gp120 in the rat neocortex

Mauro Maccarrone, Silvia Piccirilli, Natalia Battista, Claudio Del Duca, Giuseppe Nappi, M. Tiziana Corasaniti, Alessandro Finazzi-Agrò, Giacinto Bagetta

Research output: Contribution to journalArticle

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 (∼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.

Original languageEnglish
Pages (from-to)1293-1300
Number of pages8
JournalJournal of Neurochemistry
Volume89
Issue number5
DOIs
Publication statusPublished - Jun 2004

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Keywords

  • Endocannabinoids
  • Gp120
  • Lipoxygenase
  • Neuronal apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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