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标题：Dysregulated Ca²⁺ Homeostasis in Fanconi anemia cells
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作者：Cesare Usai ; Silvia Ravera ; Paola Cuccarolo 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
DOI：10.1038/srep08088
出版社：Springer Nature
摘要：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 ([Ca²⁺]_i) in resting conditions. This condition affects cellular responses to stress. The flux of Ca²⁺ mobilized by H₂O₂ from internal stores is significantly lower in FANCA cells in comparison to controls. The low basal [Ca²⁺]_i in FANCA appears to be an actively maintained process controlled by a finely tuned interplay between different intracellular Ca²⁺ stores. The defects associated with the altered Ca²⁺ homeostasis appear consistently overlapping those related to the unbalanced oxidative metabolism in FA cells underlining a contiguity between oxidative stress and calcium homeostasis.