title: Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations.
abstract: Pseudoxanthoma elasticum (PXE) is a genetic disease characterized by calcification and fragmentation of elastic fibres of the skin, cardiovascular system and eye, caused by mutations of the ABCC6 gene, which encodes the membrane transporter MRP6. The pathogenesis of the lesions is unknown. Based on studies of similar clinical and histopathological damage present in haemolytic disorders, our working hypothesis is that PXE lesions may result from chronic oxidative stress occurring in PXE cells as a consequence of MRP6 deficiency. Our results show that PXE fibroblasts suffer from mild chronic oxidative stress due to the imbalance between production and degradation of oxidant species. The findings also show that this imbalance results, at least in part, from the loss of mitochondrial membrane potential (DeltaPsi(m)) with overproduction of H2O2. Whether mitochondrial dysfunction is the main factor responsible for the oxidative stress in PXE cells remains to be elucidated. However, mild chronic generalized oxidative stress could explain the great majority of structural and biochemical alterations already reported in PXE.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena 41100, Italy. ronchetti.ivonne@unimore.it
authors.forename: Ivonne
authors.initials: I
authors.lastname: Pasquali-Ronchetti
authors.forename: Maria Inmaculada
authors.initials: MI
authors.lastname: Garcia-Fernandez
authors.forename: Federica
authors.initials: F
authors.lastname: Boraldi
authors.forename: Daniela
authors.initials: D
authors.lastname: Quaglino
authors.forename: Dealba
authors.initials: D
authors.lastname: Gheduzzi
authors.forename: Chiara
authors.initials: C
authors.lastname: De Vincenzi Paolinelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Tiozzo
authors.forename: Stefania
authors.initials: S
authors.lastname: Bergamini
authors.forename: Daniela
authors.initials: D
authors.lastname: Ceccarelli
authors.forename: Umberto
authors.initials: U
authors.lastname: Muscatello
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency; D018384:Oxidative Stress / Q000502:physiology*; D011561:Pseudoxanthoma Elasticum / Q000473:pathology / Q000503:physiopathology*; D012867:Skin / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D000975:Antioxidants; D015415:Biomarkers; D005978:Glutathione; D019803:Glutathione Disulfide; D006861:Hydrogen Peroxide; D008315:Malondialdehyde; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013482:Superoxide Dismutase; C102029:ABCC6 protein, human