Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells |
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Authors: | Toshiya Sugino Mitsuhisa Maruyama Atsushi Kuno Yoshiyuki Horio |
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Institution: | a Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556, Japan b Department of Neurosurgery, Sapporo Medical University, Sapporo 060-8556, Japan c Second Department of Internal Medicine, Sapporo Medical University, Sapporo 060-8556, Japan |
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Abstract: | SIRT1, a NAD+-dependent protein deacetylase, is known to have neural functions. However, despite its cytoplasmic expression in some neural cells, its cytoplasmic function, if any, is unknown. Here we found that PC12 (pheochromocytoma) cells expressed SIRT1 in the cytoplasm. Nerve growth factor (NGF)-induced neurite outgrowth of these cells was promoted by activators of SIRT1, while inhibitors of SIRT1 or SIRT1-siRNA significantly inhibited it. The overexpression of a mutant SIRT1 that localised to the cytoplasm but not the nucleus enhanced the NGF-dependent neurite outgrowth, and a cytoplasmic dominant-negative SIRT1 suppressed it. Thus, cytoplasmic SIRT1 increases the NGF-induced neurite outgrowth of PC12 cells. |
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Keywords: | SIRT1 Neurite outgrowth PC12 cell NGF |
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