A proteomic approach to the bilirubin‐induced toxicity in neuronal cells reveals a protective function of DJ‐1 protein |
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Authors: | Marta Deganuto Laura Cesaratto Cristina Bellarosa Raffaella Calligaris Sandra Vilotti Giovanni Renzone Rossana Foti Andrea Scaloni Stefano Gustincich Franco Quadrifoglio Claudio Tiribelli Gianluca Tell |
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Affiliation: | 1. Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy;2. Centro Studi Fegato, AREA Science Park, Basovizza, Trieste, Italy;3. Sector of Neurobiology, International School for Advanced Studies, AREA Science Park, Basovizza, Trieste, Italy;4. Proteomics and Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy;5. Department ACADEM, University of Trieste, Trieste, Italy |
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Abstract: | Unconjugated bilirubin (UCB) is a powerful antioxidant and a modulator of cell growth through the interaction with several signal transduction pathways. Although newborns develop a physiological jaundice, in case of severe hyperbilirubinemia UCB may become neurotoxic causing severe long‐term neuronal damages, also known as bilirubin encephalopathy. To investigate the mechanisms of UCB‐induced neuronal toxicity, we used the human neuroblastoma cell line SH‐SY5Y as an in vitro model system. We verified that UCB caused cell death, in part due to oxidative stress, which leads to DNA damage and cell growth reduction. The mechanisms of cytotoxicity and cell adaptation to UCB were studied through a proteomic approach that identified differentially expressed proteins involved in cell proliferation, intracellular trafficking, protein degradation and oxidative stress response. In particular, the results indicated that cells exposed to UCB undertake an adaptive response that involves DJ‐1, a multifunctional neuroprotective protein, crucial for cellular oxidative stress homeostasis. This study sheds light on the mechanisms of bilirubin‐induced neurotoxicity and might help to design a strategy to prevent or ameliorate the neuronal damages leading to bilirubin encephalopathy. |
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Keywords: | Bilirubin Cell biology Cytotoxicity Oxidative stress |
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