SIRT1 silencing confers neuroprotection through IGF‐1 pathway activation |
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| Authors: | Luigi Sansone Valentina Reali Laura Pellegrini Lidia Villanova Michele Aventaggiato Gabriella Marfe Roberta Rosa Marcella Nebbioso Marco Tafani Massimo Fini Matteo A. Russo Bruna Pucci |
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| Affiliation: | 1. Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy;2. Department of Cellular and Molecular Pathology, IRCCS San Raffaele Pisana, Rome, Italy;3. University of Hawaii Cancer Center, Department of Cancer Biology, University of Hawaii, Honolulu, Hawaii;4. Department of Medicine, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, California;5. Department of Experimental Medicine and Biochemical Sciences, “Tor Vergata” University of Rome, Rome, Italy;6. Departments of Endocrinology and Molecular and Clinical Oncology, University of Naples Federico II, Naples, Italy;7. Departments of Surgical Oncology and Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas;8. Department of Sense Organs, Centre of Ocular Electrophysiology, “Sapienza”, University of Rome, Rome, Italy |
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| Abstract: | The following study demonstrated that, in in vitro differentiated neurons, SIRT1 silencing induced an increase of IGF‐1 protein expression and secretion and of IGF‐1R protein levels which, in turn, prolonged neuronal cell survival in presence of an apoptotic insult. On the contrary, SIRT1 overexpression increased cell death. In particular, IGF‐1 and IGF‐1R expression levels were negatively regulated by SIRT1. In SIRT1 silenced cells, the increase in IGF‐1 and IGF‐1R expression was associated to an increase in AKT and ERK1/2 phosphorylation. Moreover, neuronal differentiation was reduced in SIRT1 overexpressing cells and increased in SIRT1 silenced cells. We conclude that SIRT1 silenced neurons appear more committed to differentiation and more resistant to cell death through the activation of IGF‐1 survival pathway. J. Cell. Physiol. 228: 1754–1761, 2013. © 2013 Wiley Periodicals, Inc. |
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