title: Altered expression pattern of Nrf2/HO-1 axis during accelerated-senescence in HIV-1 transgenic rat.
abstract: Chronic oxidative stress plays a central role in the pathogenesis of many diseases, including HIV-1 associated disorders. Concomitantly with the decline of endogenous antioxidant systems, it was reported that HIV-1-related proteins increase the production of radical species in cells and tissues that are not directly infected by the virus. In the context of HIV-1 infection, the role of Nrf2, a key transcription factor that contributes to the maintenance of cellular redox homeostasis, remains largely uncharacterized. One of the major stress-responsive player regulated by Nrf2 is the antioxidant enzyme HO-1. The Nrf2/HO-1 axis constitutes a crucial cell survival mechanism to counteract oxidative stress and inflammation. The present study aims to investigate the age-related patterns of Nrf2 and HO-1 in different brain regions and tissues of HIV-1 transgenic rat. Since HIV-1 induces an accelerated aging and the redox imbalance may actively promote senescence, we also evaluated the senescence phenotype-switching by quantifying levels of β-galactosidase activity. Our results showed changes in gene expression, with different trends depending on the brain regions and tissues examined. However, compared to age-matched controls, we observed in HIV-1 transgenic rats a significant reduction in the protein levels of Nrf2 and HO-1, suggesting a weakening in the protection exerted by Nrf2/HO-1 system. Moreover, we show that senescence occurs more rapidly in HIV-1 transgenic rats than in control animals. To our knowledge this is the first in vivo report showing the involvement of Nrf2/HO-1 pathway in a rat model of HIV-1.
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Davinelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scapagnini
authors.forename: Frank
authors.initials: F
authors.lastname: Denaro
authors.forename: Vittorio
authors.initials: V
authors.lastname: Calabrese
authors.forename: Francesca
authors.initials: F
authors.lastname: Benedetti
authors.forename: Selvi
authors.initials: S
authors.lastname: Krishnan
authors.forename: Sabrina
authors.initials: S
authors.lastname: Curreli
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryant
authors.forename: Davide
authors.initials: D
authors.lastname: Zella
mesh_terms: D019588:Aging, Premature / Q000209:etiology* / Q000378:metabolism / Q000821:virology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D005814:Genes, Viral; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D013154:Spleen / Q000378:metabolism / Q000821:virology
chemical_list: D054298:Human Immunodeficiency Virus Proteins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat