RESEARCH ARTICLE Altered expression pattern of Nrf2/HO-1 axis during accelerated-senescence in HIV-1 transgenic rat Sergio Davinelli • Giovanni Scapagnini • Frank Denaro • Vittorio Calabrese • Francesca Benedetti • Selvi Krishnan • Sabrina Curreli • Joseph Bryant • Davide Zella Received: 25 January 2014 / Accepted: 23 June 2014 / Published online: 16 July 2014 Ó Springer Science+Business Media Dordrecht 2014 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 b-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 reduc- tion 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 path- way in a rat model of HIV-1. Keywords Nuclear factor erythroid 2-related factor 2 Á Heme oxygenase-1 Á Human immunodeficiency virus-1 Á Senescence Introduction Substantial advances have been made over the past three decades to elucidate the complex pathobiological events related to the acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus-1 (HIV-1). Multiple studies have shown that constitutive production of inflammatory mediators and radical species may significantly contribute to the severity and S. Davinelli Á F. Benedetti Á S. Krishnan Á S. Curreli Á J. Bryant Á D. Zella Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA S. Davinelli Á G. Scapagnini (&) Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy e-mail: g.scapagnini@gmail.com F. Denaro Department of Biology, Morgan State University, Baltimore 21251, USA V. Calabrese Department of Chemistry, University of Catania, 95125 Catania, Italy 123 Biogerontology (2014) 15:449–461 DOI 10.1007/s10522-014-9511-6