TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use.
J Neurovirol
; 27(3): 367-378, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33876414
ABSTRACT
In the brain, both HIV-1 and methamphetamine (meth) use result in increases in oxidative and nitrosative stress. This redox stress is thought to contribute to the pathogenesis of HIV-associated neurocognitive disorder (HAND) and further worsening cognitive activity in the setting of drug abuse. One consequence of such redox stress is aberrant protein S-nitrosylation, derived from nitric oxide, which may disrupt normal protein activity. Here, we report an improved, mass spectrometry-based technique to assess S-nitrosylated protein in human postmortem brains using selective enrichment of S-nitrosocysteine residues with an organomercury resin. The data show increasing S-nitrosylation of tricarboxylic acid (TCA) enzymes in the setting of HAND and HAND/meth use compared with HIV+ control brains without CNS pathology. The consequence is systematic inhibition of multiple TCA cycle enzymes, resulting in energy collapse that can contribute to the neuronal and synaptic damage observed in HAND and meth use.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Processamento de Proteína Pós-Traducional
/
Ciclo do Ácido Cítrico
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Transtornos Relacionados ao Uso de Substâncias
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Disfunção Cognitiva
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Metanfetamina
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article