Involvement of Nitric Oxide in the Mitochondrial Action of Efavirenz: A Differential Effect on Neurons and Glial Cells

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 synth...

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Bibliographic Details
Published in:The Journal of infectious diseases 2015-06, Vol.211 (12), p.1953-1958
Main Authors: Apostolova, Nadezda, Funes, Haryes A., Blas-Garcia, Ana, Alegre, Fernando, Polo, Miriam, Esplugues, Juan V.
Format: Article
Language:English
Subjects:
Anti-HIV Agents - toxicity
Benzoxazines - toxicity
Cell Line
HIV/AIDS
Humans
Mitochondria - metabolism
Neuroglia - metabolism
Neurons - metabolism
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - antagonists & inhibitors
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiu825