SIRT1 silencing confers neuroprotection through IGF-1 pathway activation.
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.
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Luigi
L
Sansone
Valentina
V
Reali
Laura
L
Pellegrini
Lidia
L
Villanova
Michele
M
Aventaggiato
Gabriella
G
Marfe
Roberta
R
Rosa
Marcella
M
Nebbioso
Marco
M
Tafani
Massimo
M
Fini
Matteo A
MA
Russo
Bruna
B
Pucci
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival; D015536:Down-Regulation / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; C470545:Sirt1 protein, mouse; C488368:Sirt1 protein, rat; D056564:Sirtuin 1