Peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension.

PEROXIREDOXIN-2 PLAYS A PIVOTAL ROLE AS MULTIMODAL CYTOPROTECTOR IN THE EARLY PHASE OF PULMONARY HYPERTENSION. Free Radic Biol Med. 2017 Aug 08;: Authors: Federti E, Matte' A, Ghigo A, Andolfo I, James C, Siciliano A, Leboeuf C, Janin A, Manna F, Choi SY, Iolascon A, Beneduce E, Melisi D, Kim DW, Levi S, De Franceschi L Abstract Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homestasis is yet to be fully defined. Here, we showed that Prx2(-/-) mice displayed chronic lung inflammatory disease associated with (i) abnormal pulmonary vascular dysfunction; and (ii) increased markers of extracellular-matrix remodeling. Hypoxia was used to induce PAH. We focused on the early phase PAH to dissect the role of Prx2 in generation of PAH. Hypoxic Prx2(-/-)mice showed (i) amplified inflammatory response combined with cytokine storm; (ii) vascular activation and dysfunction; (iii) increased PDGF-B lung levels, as marker of extracellular-matrix deposition and remodeling; and (iv) ER stress with activation of UPR system and autophagy. Rescue experiments with in vivo the administration of fused-recombinant-PEP-Prx2 show a reduction in pulmonary inflammatory vasculopathy and in ER stress with down-regulation of autophagy. Thus, we propose Prx2 ...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research