Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells.
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.
Sugino
Toshiya
T
Department of Pharmacology, Sapporo Medical University, Chuo-ku, Sapporo, Japan.
Maruyama
Mitsuhisa
M
Tanno
Masaya
M
Kuno
Atsushi
A
Houkin
Kiyohiro
K
Horio
Yoshiyuki
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D009243:NAD / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology
D009414:Nerve Growth Factors; D013267:Stilbenes; D009243:NAD; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol