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RESEARCH PRODUCT
Involvement of nitric oxide in the mitochondrial action of efavirenz: a differential effect on neurons and glial cells
Haryes A. FunesNadezda ApostolovaMiriam PoloFernando AlegreJuan V. EspluguesAna Blas-garciasubject
CyclopropanesNNRTIEfavirenzAnti-HIV AgentsCentral nervous systemNitric Oxide Synthase Type IIMitochondrionBiologyNitric OxideNitric oxideCell Linechemistry.chemical_compoundMediatornitric oxidemedicineImmunology and AllergyHumansNeuronsNeurotoxicityelectron transport chainHIVefavirenzmedicine.diseasecentral nervous systemCell biologyBenzoxazinesMitochondriaNitric oxide synthasemitochondriaInfectious Diseasesmedicine.anatomical_structurechemistryAlkynesImmunologybiology.proteinNeurogliaNeurogliadescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-07-10 |