Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene, however the pathogenetic mechanisms leading to elastic fibre calcification and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. In conclusion, these data shed new light on pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlighting the role of several differentially expressed proteins that could be regarded as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, these data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations.

Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum / Boraldi, Federica; Annovi, Giulia; Guerra, Deanna; Paolinelli Devincenzi, Chiara; Maria Inmaculada Garcia, Fernandez; Panico, Fulvio; De Santis, Giorgio; Tiozzo, Roberta; Ronchetti, Ivonne; Quaglino, Daniela. - In: PROTEOMICS. CLINICAL APPLICATIONS. - ISSN 1862-8346. - STAMPA. - 3(9)(2009), pp. 1084-1098. [10.1002/prca.200900007]

Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum

BORALDI, Federica;ANNOVI, Giulia;GUERRA, Deanna;PAOLINELLI DEVINCENZI, Chiara;PANICO, Fulvio;DE SANTIS, Giorgio;TIOZZO, Roberta;RONCHETTI, Ivonne;QUAGLINO, Daniela
2009

Abstract

Pseudoxanthoma elasticum (PXE) is a genetic disorder associated to mutations in the ABCC6 gene, however the pathogenetic mechanisms leading to elastic fibre calcification and to clinical manifestations are still unknown. Dermal fibroblasts, directly involved in the production of the extracellular milieu, have been isolated from healthy subjects and from patients affected by PXE, cultured in vitro and characterized for their ability to produce reactive oxygen species, for structural and functional properties of their cell membranes, for changes in their protein profile. Data demonstrate that oxidative stress has profound and endurable consequences on PXE fibroblast phenotype being responsible for: reduced levels of global DNA methylation, increased amount of carbonylated proteins and of lipid peroxidation products, altered structural properties of cell membranes, modified protein expression. In conclusion, these data shed new light on pathogenetic pathways in PXE, by identifying a network of proteins affecting elastic fibre calcification through inefficient vitamin K recycling, and highlighting the role of several differentially expressed proteins that could be regarded as targets for validating the efficacy of future therapeutic strategies aiming to delay and/or revert the pathologic phenotype of PXE fibroblasts. Moreover, these data open new perspectives for investigating PXE-like phenotypes in the absence of ABCC6 mutations.
3(9)
1084
1098
Fibroblast protein profile analysis highlights the role of oxidative stress and vitamin K recycling in the pathogenesis of pseudoxanthoma elasticum / Boraldi, Federica; Annovi, Giulia; Guerra, Deanna; Paolinelli Devincenzi, Chiara; Maria Inmaculada Garcia, Fernandez; Panico, Fulvio; De Santis, Giorgio; Tiozzo, Roberta; Ronchetti, Ivonne; Quaglino, Daniela. - In: PROTEOMICS. CLINICAL APPLICATIONS. - ISSN 1862-8346. - STAMPA. - 3(9)(2009), pp. 1084-1098. [10.1002/prca.200900007]
Boraldi, Federica; Annovi, Giulia; Guerra, Deanna; Paolinelli Devincenzi, Chiara; Maria Inmaculada Garcia, Fernandez; Panico, Fulvio; De Santis, Giorgio; Tiozzo, Roberta; Ronchetti, Ivonne; Quaglino, Daniela
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/640905
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