Interactions between Integrase Inhibitors and human Arginase 1

Lucia Lisi, Pierluigi Navarra, Michela Pizzoferrato, Fabiola Teresa Miscioscia, Alessandra Topai

Risultato della ricerca: Contributo in rivistaArticolo in rivista

2 Citazioni (Scopus)

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 for 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 the present study, we investigated whether Integrase Strand Transfer Inhibitors (INSTIs) 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 (CHME-5), 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 INSTIs in this newly validated model. Overall evidence shows that Dolutegravir, Raltegravir and Elvitegravir inhibit ARG activity
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaJournal of Neurochemistry
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Arginase 1
  • Integrase Strand Transfer Inhibitors
  • microglia

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