title: Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells.
abstract: The anti-human immunodeficiency virus (HIV) drug efavirenz (EFV) alters mitochondrial function in cultured neurons and glial cells. Nitric oxide (NO) is a mediator of mitochondrial dysfunction associated with HIV central nervous system symptoms. We show that EFV promotes inducible nitric oxide synthase (iNOS) expression in cultured glial cells and generated NO undermines their mitochondrial function, as inhibition of NOS partially reverses this effect. EFV inhibits mitochondrial Complex I in both neurons and glia; however, when the latter cells are treated for longer periods, other mitochondrial complexes are also affected in accordance with the increased NO production. These findings shed light on the mechanisms responsible for the frequent EFV-associated neurotoxicity.
authors.affiliation: Facultad de Ciencias de la Salud, Universitat Jaume I, Castellón de la Plana CIBERehd, Valencia.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Apostolova
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia.
authors.forename: Haryes A
authors.initials: HA
authors.lastname: Funes
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia FISABIO-Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Blas-Garcia
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia FISABIO-Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alegre
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia FISABIO-Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Polo
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia CIBERehd, Valencia FISABIO-Hospital Universitario Dr. Peset, Valencia, Spain.
authors.forename: Juan V
authors.initials: JV
authors.lastname: Esplugues
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000633:toxicity; D048588:Benzoxazines / Q000633:toxicity*; D002460:Cell Line; D003521:Cyclopropanes; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C098320:efavirenz
keywords: HIV; NNRTI; central nervous system; efavirenz; electron transport chain; mitochondria; nitric oxide