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Interactions between integrase inhibitors and human arginase 1
Author(s) -
Lisi Lucia,
Pizzoferrato Michela,
Miscioscia Fabiola Teresa,
Topai Alessandra,
Navarra Pierluigi
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14039
Subject(s) - raltegravir , arginase , integrase , elvitegravir , integrase inhibitor , dolutegravir , context (archaeology) , microglia , arginine , chemistry , biochemistry , in vitro , biology , microbiology and biotechnology , pharmacology , human immunodeficiency virus (hiv) , inflammation , virology , antiretroviral therapy , immunology , gene , viral load , paleontology , amino acid
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.