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J Infect Dis. 2015 Jun 15;211(12):1953-8. doi: 10.1093/infdis/jiu825. Epub 2014 Dec 23.

Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells.

Author information

1
Facultad de Ciencias de la Salud, Universitat Jaume I, Castellón de la Plana CIBERehd, Valencia.
2
Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia.
3
Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia FISABIO-Hospital Universitario Dr. Peset, Valencia, Spain.
4
Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia CIBERehd, Valencia FISABIO-Hospital Universitario Dr. Peset, Valencia, Spain.

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.

KEYWORDS:

HIV; NNRTI; central nervous system; efavirenz; electron transport chain; mitochondria; nitric oxide

PMID:
25538272
DOI:
10.1093/infdis/jiu825
[Indexed for MEDLINE]

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