Inhibition of metalloproteinase activity in FANCA Is linked to altered oxygen metabolism

Silvia Ravera, Cristina Capanni, Danika Tognotti, Roberta Bottega, Marta Columbaro, Carlo Dufour, Enrico Cappelli, Paolo Degan

Research output: Contribution to journalArticle

Abstract

Bone marrow (BM) failure, increased risk of myelodysplastic syndrome, acute leukaemia and solid tumors, endocrinopathies and congenital abnormalities are the major clinical problems in Fanconi anemia patients (FA). Chromosome instability and DNA repair defects are the cellular characteristics used for the clinical diagnosis. However, these biological defects are not sufficient to explain all the clinical phenotype of FA patients. The known defects are structural alteration in cell cytoskeleton, altered structural organization for intermediate filaments, nuclear lamina, and mitochondria. These are associated with different expression and/or maturation of the structural proteins vimentin, mitofilin, and lamin A/C suggesting the involvement of metalloproteinases (MPs). Matrix metalloproteinases (MMP) are involved in normal physiological processes such as human skeletal tissue development, maturation, and hematopoietic reconstitution after bone marrow suppression. Current observations upon the eventual role of MPs in FA cells are largely inconclusive. We evaluated the overall MPs activity in FA complementation group A (FANCA) cells by exposing them to the antioxidants N-acetyl cysteine (NAC) and resveratrol (RV). This work supports the hypothesis that treatment of Fanconi patients with antioxidants may be important in FA therapy.

Original languageEnglish
Pages (from-to)603-609
Number of pages7
JournalJournal of Cellular Physiology
Volume230
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Metalloproteases
Metabolism
Fanconi Anemia
Oxygen
Defects
Bone
Antioxidants
Acetylcysteine
Lamin Type A
Mitochondria
Vimentin
Chromosomes
Matrix Metalloproteinases
Tumors
Repair
Tissue
Bone Marrow
Nuclear Lamina
Physiological Phenomena
DNA

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Medicine(all)

Cite this

Inhibition of metalloproteinase activity in FANCA Is linked to altered oxygen metabolism. / Ravera, Silvia; Capanni, Cristina; Tognotti, Danika; Bottega, Roberta; Columbaro, Marta; Dufour, Carlo; Cappelli, Enrico; Degan, Paolo.

In: Journal of Cellular Physiology, Vol. 230, No. 3, 01.03.2015, p. 603-609.

Research output: Contribution to journalArticle

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