title: Dysregulated Ca2+ homeostasis in Fanconi anemia cells.
abstract: Fanconi Anemia (FA) is a rare and complex inherited blood disorder associated with bone marrow failure and malignancies. Many alterations in FA physiology appear linked to red-ox unbalance including alterations in the morphology and structure of nuclei, intermediate filaments and mitochondria, defective respiration, reduced ATP production and altered ATP/AMP ratio. These defects are consistently associated with impaired oxygen metabolism indeed treatment with antioxidants N-acetylcysteine (NAC) and resveratrol (RV) does rescue FA physiology. Due to the importance of the intracellular calcium signaling and its key function in the control of intracellular functions we were interested to study calcium homeostasis in FA. We found that FANCA cells display a dramatically low intracellular calcium concentration ([Ca(2+)]i) in resting conditions. This condition affects cellular responses to stress. The flux of Ca(2+) mobilized by H2O2 from internal stores is significantly lower in FANCA cells in comparison to controls. The low basal [Ca(2+)]i in FANCA appears to be an actively maintained process controlled by a finely tuned interplay between different intracellular Ca(2+) stores. The defects associated with the altered Ca(2+) homeostasis appear consistently overlapping those related to the unbalanced oxidative metabolism in FA cells underlining a contiguity between oxidative stress and calcium homeostasis.
authors: Institute of Biophysics, National Research Council, 16149 Genova, Italy.
authors: Cesare
authors: C
authors: Usai
authors: DIFAR-Biochemistry Lab., Department of Pharmacology, University of Genova, 16132 Genova, Italy.
authors: Silvia
authors: S
authors: Ravera
authors: S. C. Mutagenesis, IRCCS AOU San Martino - IST (Istituto Nazionale per la Ricerca sul Cancro), CBA Torre A2, 16123 Genova, Italy.
authors: Paola
authors: P
authors: Cuccarolo
authors: DIFAR-Biochemistry Lab., Department of Pharmacology, University of Genova, 16132 Genova, Italy.
authors: Isabella
authors: I
authors: Panfoli
authors: Hematology Unit, Istituto Giannina Gaslini, 16148 Genova, Italy.
authors: Carlo
authors: C
authors: Dufour
authors: Hematology Unit, Istituto Giannina Gaslini, 16148 Genova, Italy.
authors: Enrico
authors: E
authors: Cappelli
authors: S. C. Mutagenesis, IRCCS AOU San Martino - IST (Istituto Nazionale per la Ricerca sul Cancro), CBA Torre A2, 16123 Genova, Italy.
authors: Paolo
authors: P
authors: Degan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D002460:Cell Line; D005199:Fanconi Anemia / Q000378:metabolism* / Q000473:pathology*; D051856:Fanconi Anemia Complementation Group Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006575:Heterocyclic Compounds, 3-Ring / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002232:Carbocyanines; D051856:Fanconi Anemia Complementation Group Proteins; D006575:Heterocyclic Compounds, 3-Ring; D013267:Stilbenes; C068483:rhod-2; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine; D019284:Thapsigargin; D006861:Hydrogen Peroxide; D000252:Calcium-Transporting ATPases; D000077185:Resveratrol; D002118:Calcium; D000111:Acetylcysteine
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