Interactions between integrase inhibitors and human arginase 1.
J Neurochem
; 142(1): 153-159, 2017 07.
Article
en En
| MEDLINE
| ID: mdl-28397245
ABSTRACT
The neuro-pathogenic mechanism(s) underlying HIV-associated neurocognitive disorders are mostly unknown. HIV-infected macrophages and microglial cells play a crucial role and the metabolic fate of l-arginine may be highly relevant to microglia activation. In this context, arginase (ARG), which uses l-arginine as substrate, can be on the same time a target and source of oxidative stress and inflammation. In this study, we investigated whether integrase strand transfer inhibitors share with the other antiretroviral drugs the ability to inhibit ARG activity. We used the previously validated cell model, namely the human microglia cell line, as well as the computational chemistry approach. Furthermore, here we characterized the activity of purified human ARG in a cell-free in vitro system, and investigated the effects of integrase strand transfer inhibitors in this newly validated model. Overall evidence shows that Dolutegravir, Raltegravir and Elvitegravir inhibit ARG activity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Arginasa
/
Inhibidores de Integrasa VIH
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article