title: Potential neuroprotective effects of SIRT1 induced by glucose deprivation in PC12 cells.
abstract: Nutrient availability is one of the most important signals regulating cellular fates including cell growth, differentiation, and death. Recent evidence suggests that the NAD(+)-dependent histone deacetylase sirtuin 1 (SIRT1) plays a prominent role in linking changes in nutritional availability with cellular fate regulation. SIRT1 expression is observed in neurons, yet the expressional and functional regulation of this protein is not fully understood. In the present study, we examined whether extracellular glucose concentration affects the expression and localization of SIRT1 in PC12 cells. Further, we examined levels of forkhead box O3a (FoxO3a), which is also controlled by changes in extracellular glucose concentration. We observed the total expression levels of SIRT1 and FoxO3a in PC12 cells were reduced when glucose availability increased via gene expressional control, at least in part. Nuclear localization of SIRT1 and FoxO3a was increased by glucose deprivation. Even though the changes in extracellular glucose concentration regulated SIRT1 and FoxO3a in a similar direction, the effects of nerve growth factor on these two proteins were completely different. Finally, we found the potent SIRT1 inhibitor enhanced glucose deprivation-induced cell death. Therefore, we propose that glucose deprivation-induced SIRT1 expression potentially plays a major role in protecting PC12 cells.
authors.affiliation: Department of Life Sciences, Graduate School of Life Sciences, Toyo University, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fujino
authors.forename: Yurina
authors.initials: Y
authors.lastname: Ogura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sato
authors.forename: Taku
authors.initials: T
authors.lastname: Nedachi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005947:Glucose / Q000172:deficiency*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose
keywords: BCA; BSA; DMEM; Dulbecco's modified Eagle's medium; FOXO; FoxO3a; Glucose; LDH; NGF; Nerve growth factor; PBS; PC12; PI3K; RT; SIRT1; Sir2; Tbs; bicinchoninic acid assay; bovine serum albumin; forkhead transcription factor O; lactate dehydrogenase; nerve growth factor; phosphate-buffered saline; phosphatidylinositol 3-kinase; room temperature; silent information regulator 2; sirtuin 1; tris-buffered saline