title: Oxidative stress and antioxidant response in fibroblasts from Werner and atypical Werner syndromes.
abstract: Werner Syndrome (WS, ICD-10 E34.8, ORPHA902) and Atypical Werner Syndrome (AWS, ICD-10 E34.8, ORPHA79474) are very rare inherited syndromes characterized by premature aging. While approximately 90% of WS individuals have any of a range of mutations in theWRN gene, there exists a clinical subgroup in which the mutation occurs in the LMNA/C gene in heterozygosity. Although both syndromes exhibit an age-related pleiotropic phenotype, AWS manifests the onset of the disease during childhood, while major symptoms in WS appear between the ages of 20 and 30. To study the molecular mechanisms of progeroid diseases provides a useful insight into the normal aging process. Main changes found were the decrease in Cu/Zn and Mn SOD activities in the three cell lines. In AWS, both mRNA SOD and protein levels were also decreased. Catalase and glutathione peroxidases decrease, mainly in AWS. Glutaredoxin (Grx) and thioredoxin (Trx) protein expression was lower in the three progeroid cell lines. Grx and Trx were subjected to post-transcriptional regulation, because protein expression was reduced although mRNA levels were not greatly affected in WS. Low antioxidant defense and oxidative stress occur simultaneously in these rare genetic instability disorders at the onset of progeroid disease.
authors.affiliation: CIBERER. Centro de Investigación Biomédica en Red de Enfermedades Raras, Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Seco-Cervera
authors.forename: Marta
authors.initials: M
authors.lastname: Spis
authors.forename: José Luis
authors.initials: JL
authors.lastname: García-Giménez
authors.forename: José Santiago
authors.initials: JS
authors.lastname: Ibañez-Cabellos
authors.forename: Ana
authors.initials: A
authors.lastname: Velázquez-Ledesma
authors.forename: Isabel
authors.initials: I
authors.lastname: Esmorís
authors.forename: Sergio
authors.initials: S
authors.lastname: Bañuls
authors.forename: Giselle
authors.initials: G
authors.lastname: Pérez-Machado
authors.affiliation: Department of Physiology, Medicine School, University of Valencia, Valencia. Spain.
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
mesh_terms: D000293:Adolescent; D000328:Adult; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000975:Antioxidants / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D002648:Child; D005090:Exodeoxyribonucleases / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D008297:Male; D009154:Mutation; D018384:Oxidative Stress; D011371:Progeria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071657:Werner Syndrome Helicase; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D005090:Exodeoxyribonucleases; D005978:Glutathione; D034904:Lamin Type A; D012333:RNA, Messenger; D053484:RecQ Helicases; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000071657:Werner Syndrome Helicase; D000099156:Superoxide Dismutase 2; C494847:LMNA protein, human; C000606290:SOD1 protein, human; C098785:WRN protein, human