Pseudoxanthoma elasticum: oxidative stress and antioxidant diet in a mouse model (Abcc6-/-)

J Invest Dermatol. 2008 May;128(5):1160-4. doi: 10.1038/sj.jid.5701145. Epub 2007 Nov 29.

Abstract

Pseudoxanthoma elasticum (PXE), a multisystem disorder characterized by ectopic mineralization of soft connective tissues, is caused by mutations in the ABCC6 gene. The pathomechanistic details of the mineralization process are largely unknown, but oxidative stress has been suggested to play a role. In this study, we tested Abcc6(-/-) mice, which serve as a model of PXE, for markers of the oxidative stress in the liver and serum. The total antioxidant capacity as well as markers of protein oxidation and lipid peroxidation suggested the presence of chronic oxidative stress. Feeding these mice for 5 months with a diet supplemented with antioxidants (vitamins C and E, selenium, and N-acetylcysteine) countered the oxidative stress but did not modify the ectopic mineralization process. These results suggest that the Abcc6(-/-) mice suffer from chronic oxidative stress but this does not contribute to connective tissue mineralization, the hallmark of PXE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Animal Feed
  • Animals
  • Antioxidants / pharmacology*
  • Connective Tissue / metabolism
  • Connective Tissue / pathology
  • Disease Models, Animal
  • Lipid Peroxidation
  • Mice
  • Mice, Knockout
  • Multidrug Resistance-Associated Proteins
  • Oxidative Stress*
  • Pseudoxanthoma Elasticum / diet therapy*
  • Pseudoxanthoma Elasticum / genetics
  • Pseudoxanthoma Elasticum / metabolism*
  • Pseudoxanthoma Elasticum / pathology
  • Skin / metabolism
  • Skin / pathology

Substances

  • ATP-Binding Cassette Transporters
  • Abcc6 protein, mouse
  • Antioxidants
  • Multidrug Resistance-Associated Proteins