ABSTRACT
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. Several evidences suggest that MS can be considered a multi-factorial disease in which both genetics and environmental factors are involved. Among proposed candidates, growing results support the involvement of oxidative stress (OS) in MS pathology. The aim of this study was to investigate the role of OS in event of exacerbations in MS on serum of relapsing-remitting (RR-MS) patients, either in relapsing or remitting phase, with respect to serum from healthy subjects. We applied proteomics and redox proteomics approaches to identify differently expressed and oxidatively modified proteins in the low-abundant serum protein fraction. Among differently expressed proteins ceruloplasmin, antithrombin III, clusterin, apolipoprotein E, and complement C3, were up-regulated in MS patients compared with healthy controls. Further by redox proteomics, vitamin D-binding protein showed a progressive trend of oxidation from remission to relapse, respect with controls. Similarly, the increase of oxidation of apolipoprotein A-IV confirmed that levels of OS are elevated with the progression of the disease. Our findings support the involvement of OS in MS and suggest that dysfunction of target proteins occurs upon oxidative damage and correlates with the pathology.
Subject(s)
Blood Proteins/metabolism , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/pathology , Oxidative Stress , Proteomics/methods , Adult , Apolipoproteins A/metabolism , Case-Control Studies , Demography , Electrophoresis, Gel, Two-Dimensional , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/metabolism , Oxidation-Reduction , Protein Carbonylation , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Vitamin D-Binding Protein/metabolismABSTRACT
Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient to induce tumour development. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues were collected from patients with invasive squamous cervical carcinoma, from patients with High Grade dysplastic HPV lesions and from patients with no clinical evidence of HPV lesions. After virological characterization, modulation of proteins involved in the redox status regulation was investigated. ERp57 and GST were sharply elevated in dysplastic and neoplastic tissues. TrxR2 peaked in dysplastic samples while iNOS was progressively reduced in dysplastic and neoplastic samples. By redox proteomic approach, five proteins were found to have increased levels of carbonyls in dysplastic samples respect to controls namely: cytokeratin 6, actin, cornulin, retinal dehydrogenase and GAPDH. In carcinoma samples the peptidyl-prolyl cis-trans isomerase A, ERp57, serpin B3, Annexin 2 and GAPDH were found less oxidized than in dysplastic tissues. HPV16 neoplastic progression seems associated with increased oxidant environment. In dysplastic tissues the oxidative modification of DNA and proteins involved in cell morphogenesis and terminal differentiation may provide the conditions for the neoplastic progression. Conversely cancer tissues seem to attain an improved control on oxidative damage as shown by the selective reduction of carbonyl adducts on key detoxifying/pro-survival proteins.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Human papillomavirus 16 , Oxidative Stress , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Neoplasms/metabolism , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Cell Transformation, Neoplastic , Electrophoresis, Gel, Two-Dimensional , Female , Glutathione Transferase/metabolism , Humans , Middle Aged , Nitric Oxide Synthase Type II/metabolism , Oxidation-Reduction , Protein Carbonylation , Protein Disulfide-Isomerases/metabolism , Proteomics , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Viral LoadABSTRACT
"High risk" HPV types have different geographical distribution and evidence suggests their respective prevalence may vary in different areas and regions. An accurate description of high-risk HPV circulation is a key feature for the rational design of prevention and screening campaigns. A cross-sectional, virological study was conducted on adult Albanian women living either in the Tirana area or in the Duress prefecture. Clinical and gynecological evaluations were performed according to current standard criteria. HPV detection and typing were carried out by a combined MY09/MY11 and GP5+/GP6+ PCR followed by direct sequencing of generated amplicons. Virological data were obtained from 402 out of 452 patients enrolled between January 2004 and December 2007. Sixty-one patients (15.1% of the cohort) were found to be infected with a genital HPV. As expected, viral prevalence was higher among women younger than 30 years of age (25.2%) in comparison to those aged 30 or older (13.6%). HPV 16 was found to be the most frequent type (41% of cases), followed by HPV 53 (7.2%), HPV 31 (5.8%), and HPV 18 (4.3%). HPV 81 and HPV 84 were the most prevalent low-risk types detected with prevalences of 11.6% and 5.8%, respectively. No differences were noted in any type-specific prevalence between young and mature women. The circulation of HPV types is far more complex than assumed generally. Detailed knowledge of HPV type circulating patterns in specific local geographical areas is essential for appropriate implementation of screening, prevention, and surveillance campaigns.
