Giovanni Pagano

Publications (75) View all

• Article: Bone Marrow Cell Transcripts from Fanconi Anaemia Patients Reveal in Vivo Alterations in Mitochondrial, Redox and DNA Repair Pathways.

  Giovanni Pagano, Annarita Aiello Talamanca, Giuseppe Castello, Marco d'Ischia, Federico V Pallardó, Sandra Petrović, Beatriz Porto, Luca Tiano, Adriana Zatterale
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  ABSTRACT: Fanconi anaemia (FA) is a genetic cancer predisposition disorder associated with cytogenetic instability, bone marrow failure, and a pleiotropic cellular phenotype including low thresholds of responses to oxidative stress, cross-linking agents, and selected cytokines. This study was aimed at defining the scope of abnormalities in gene expression using the publicly available FA Transcriptome Consortium (FTC) database (Gene Expression Omnibus, 2009 and publicly available as GSE16334). We evaluated the data set that included transcriptomal analyses on RNA obtained from low density bone marrow cells (BMC) from 20 FA patients and 11 healthy volunteers, by seeking to identify changes in expression of over 22,000 genes, including a set of genes involved in: a) bioenergetic pathways; b) antioxidant activities; c) response to stress and metal-chelating proteins; d) inflammation-related cytokines, and e) DNA repair. Ontological analysis of genes expressed at magnitudes of 1.5 fold or greater demonstrated significant suppression of genes in the categories of a) energy metabolism; b) antioxidant activities; and c) stress and chelating proteins. Enhanced expression was found for 16 of 26 genes encoding inflammatory cytokines. A set of 20 out of 21 transcripts for DNA repair activities were down-regulated; four of these transcripts related to type II topoisomerase. The data provide evidence for alterations in gene regulation of bioenergetic activities, redox-related activities, stress and metal-chelating proteins, and of some selected DNA repair activities in FA patients. This article is protected by copyright. All rights reserved.
  European Journal Of Haematology 05/2013; · 2.61 Impact Factor
• Article: From clinical description to in vitro and animal studies, and backwards to patients: Oxidative stress and mitochondrial dysfunction in Fanconi anaemia.

  Giovanni Pagano, Annarita Aiello Talamanca, Giuseppe Castello, Marco d'Ischia, Federico V Pallardó, Sandra Petrović, Beatriz Porto, Luca Tiano, Adriana Zatterale
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  ABSTRACT: Fanconi anaemia (FA) is a rare genetic disease associated to deficiencies in DNA repair pathways. A body of literature points to a prooxidant state in FA patients, along with the evidence for oxidative stress (OS) in FA phenotype reported by in vitro, molecular and animal studies. A highlight arises from the detection of mitochondrial dysfunction (MDF) in FA cell lines of complementation groups A, C, D2 and G. As yet lacking, in vivo studies should focus on FA-associated MDF that may help understanding the mitochondrial basis of OS detected in cells and body fluids from FA patients. Beyond the in vitro and animal database, the available analytical devices may prompt the direct observation of metabolic and mitochondrial alterations in FA patients. These studies should evaluate a set of MDF-related endpoints, to be related with OS endpoints. The working hypothesis is raised that, parallel to OS, nitrosative stress might be another, so far unexplored hallmark of FA phenotype. The expected results may shed light into FA pathogenesis and might provide the grounds for pilot chemoprevention trials using mitochondrial nutrients.
  Free radical biology & medicine 01/2013; · 5.42 Impact Factor
• Source

  Available from: Giovanni Pagano

  Dataset: Pallardò - mitochondria 2010 Biogerontology

  Federico V Pallardó, Ana Lloret, Michel Lebel, Marco d'Ischia, Victoria C Cogger, David G Le Couteur, Maria Nicola Gadaleta, Giuseppe Castello, Giovanni Pagano
• Article: Sjøgren's syndrome-associated oxidative stress and mitochondrial dysfunction: Prospects for chemoprevention trials.

  Giovanni Pagano, Giuseppe Castello, Federico V Pallardó
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  ABSTRACT: Abstract An involvement of oxidative stress (OS) was found in recent studies of Sjøgren's syndrome (SS) that reported significant changes in protein oxidation, myeloperoxidase activity, TNF-α, nitrotyrosine and GSH levels in plasma from SS patients. Excess levels of OS markers, as oxidative DNA damage and propanoyl-lysine were reported in saliva from SS patients. Previous reports concurred with a role of OS in SS pathogenesis, by showing a decreased expression of antioxidant activities in conjunctival epithelial cells of SS patients and in parotid gland tissue samples from SS patients. A link between OS and mitochondrial dysfunction (MDF) is recognized both on the grounds of the established role of mitochondria in reactive oxygen species (ROS) formation and by the occurrence of MDF in a set of OS-related disorders. Early studies detected mitochondrial alterations in cells from SS patients, related to the action of antimitochondrial autoantibodies, and affecting specific mitochondrial activities. Thus, a link between MDF and OS may be postulated in SS, prompting studies aimed at elucidating SS pathogenesis and in the prospect of chemoprevention trials in SS clinical management.
  Free radical research 11/2012; · 2.22 Impact Factor
• Article: Multiple Involvement of Oxidative Stress in Werner Syndrome Phenotype

  Giovanni Pagano, Adriana Zatterale, Paolo Degan, Marco d’Ischia, Frank J. Kelly, Federico V. Pallardó, Seiji Kodama
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  ABSTRACT: Werner syndrome is a genetic disease characterized by early ageing, excess cancer risk, high incidence of type II diabetes mellitus, early atherosclerosis, ocular cataracts, and osteoporosis. The protein encoded by the defective gene, WRN (WRNp) associates with three activities, that is, a RecQ DNA helicase, 3′-5′-exonuclease and ATPase activities. By highlighting the DNA helicase activity, a widespread consensus in WS-associated defect(s) has been established, pointing toward a deficiency in maintaining DNA integrity. However, a possible involvement of redox pathways in WS may be suggested by several lines of evidence that include: (i) the multiple functions and interactions of WRNp with oxidative stress-related activities and factors; (ii) the pleiotropic WS clinical phenotype encompassing a number of oxidative stress-related pathologies; (iii) redox-related toxicity mechanisms of several xenobiotics exerting excess toxicity in WS cells; (iv) recent in vivo and in vitro findings of redox abnormalities in WS patients and in WS cells. The working hypothesis is raised that a deficiency in WRNp, and the pleiotropic clinical phenotype in WS patients may provide the basis to envision an underlying in vivo prooxidant state, which causes oxidative damage to biomolecules, with multiple oxidative stress-related alterations, resulting in multi-faceted clinical consequences.
  Biogerontology 04/2012; 6(4):233-243. · 3.34 Impact Factor