title: Inhibition of metalloproteinase activity in FANCA is linked to altered oxygen metabolism.
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.
authors.affiliation: DIFAR-Biochemistry Lab., Department of Pharmacology, University of Genova, Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ravera
authors.forename: Cristina
authors.initials: C
authors.lastname: Capanni
authors.forename: Danika
authors.initials: D
authors.lastname: Tognotti
authors.forename: Roberta
authors.initials: R
authors.lastname: Bottega
authors.forename: Marta
authors.initials: M
authors.lastname: Columbaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Enrico
authors.initials: E
authors.lastname: Cappelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Degan
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D005199:Fanconi Anemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; C088548:IMMT protein, human; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D014746:Vimentin; D045726:Metalloproteases; D010100:Oxygen