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Inhibition of Metalloproteinase Activity in FANCA Is Linked to Altered Oxygen Metabolism
Author(s) -
Ravera Silvia,
Capanni Cristina,
Tognotti Danika,
Bottega Roberta,
Columbaro Marta,
Dufour Carlo,
Cappelli Enrico,
Degan Paolo
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24778
Subject(s) - fanca , fanconi anemia , lamin , biology , nuclear lamina , matrix metalloproteinase , dna damage , bone marrow failure , cancer research , microbiology and biotechnology , fancd2 , methylglyoxal , dna repair , haematopoiesis , stem cell , genetics , biochemistry , nuclear protein , enzyme , dna , gene , nucleus , transcription factor
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. J. Cell. Physiol. 230: 603–609, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company