Journal
FEBS LETTERS
Volume 584, Issue 13, Pages 2821-2826Publisher
WILEY
DOI: 10.1016/j.febslet.2010.04.063
Keywords
SIRT1; Neurite outgrowth; PC12 cell; NGF
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Japan Society for the Promotion of Science [22590245]
- Sapporo Medical University
- Grants-in-Aid for Scientific Research [22591228, 22590245] Funding Source: KAKEN
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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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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