Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders.
Brain Res
; 1458: 1-11, 2012 Jun 06.
Article
en En
| MEDLINE
| ID: mdl-22554480
ABSTRACT
Oxidative stress has been suggested to play a key role in the neuropathogenesis of HIV infection. HIV proteins (gp120, Tat) and proinflammatory cytokines can trigger the production of reactive oxygen species (ROS), resulting in DNA and RNA lesions. Among all the lesions induced by ROS, one of the most abundant lesions in DNA and RNA is 8-hydroxydeoxyguanosine (8-oxoG). Here, we studied accumulated DNA oxidative damage induced by ROS in the central nervous system (CNS) in tissue from neuro-AIDS patients. The frontal cortex of autopsy tissue from HIV-1 infected patients was adopted for analysis for HIV-1 subtype, nuclear and mitochondrial DNA lesions by immunofluorescence staining, qPCR and sequencing of PCR cloning. This study provides evidence that HIV infection in the CNS leads to nuclear and mitochondrial genomic DNA damage in the brain. High level of nuclear and mtDNA 8-oxoG damage were identified in the cortex autopsy tissue of HAND patients. Increased accumulation of mtDNA mutations and depletion occurs in brain tissue in a subset of HAND cases, and is significantly different from that observed in control cases. These findings suggest that higher level of ROS in the CNS of HAND patients would contribute to the HIV induced neuro-inflammation and apoptosis of neuronal and glial cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
ADN Mitocondrial
/
Infecciones por VIH
/
Núcleo Celular
/
VIH-1
/
Trastornos del Conocimiento
/
Lóbulo Frontal
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Brain Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
China