Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations

• Published in: The Journal of pathology Vol. 208; no. 1; pp. 54 - 61
• Main Authors: Pasquali-Ronchetti, Ivonne, Garcia-Fernandez, Maria Inmaculada, Boraldi, Federica, Quaglino, Daniela, Gheduzzi, Dealba, De Vincenzi Paolinelli, Chiara, Tiozzo, Roberta, Bergamini, Stefania, Ceccarelli, Daniela, Muscatello, Umberto
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2006; Wiley
• Subjects: Adenine Nucleotides - analysis; Adult; Antioxidants - metabolism; Biological and medical sciences; Biomarkers - analysis; Cells, Cultured; Chronic Disease; connective tissue; elastin mineralization; extracellular matrix; Female; fibroblast; Fibroblasts - physiology; Glutathione - analysis; Glutathione Disulfide - analysis; Humans; Hydrogen Peroxide - metabolism; Investigative techniques, diagnostic techniques (general aspects); Malondialdehyde - analysis; Medical sciences; Membrane Potentials - physiology; Middle Aged; Mitochondria - physiology; MRP6; Multidrug Resistance-Associated Proteins - deficiency; oxidative stress; Oxidative Stress - physiology; pathogenesis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; pseudoxanthoma elasticum (PXE); Pseudoxanthoma Elasticum - pathology; Pseudoxanthoma Elasticum - physiopathology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - pathology; Superoxide Dismutase - metabolism; Human; Oxidative stress; Skin disease; Elastic tissue disease; Pathogenesis; Elastin; Genetic disease; MRP6; Symptomatology; Connective tissue; MRP2 protein; Anatomic pathology; pseudoxanthoma elasticum (PXE); Mineralization; elastin mineralization; Extracellular matrix; Pseudoxanthoma elasticum; Fibroblast
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.1867

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 (ΔΨm) 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. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.