Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways.
Rationale: Lithium is currently used in the treatment of mental illness. We have previously reported that lithium stimulated the protein kinase B/Forkhead box O1 (Akt/FoxO1) pathway in rats. However, little information is available regarding its neuroprotective role of this pathway and underlying me...
| Publicado en: | Psychopharmacology Vol. 233; no. 5; pp. 785 - 795 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Mar2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=112926420&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 112926420 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Mar2016 vid: 233 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 112926420 10.1007/s00213-015-4168-7 112926420 ppf: 785 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways. aug: au: Zeng, Zhiwen Wang, Haitao Shang, Fu Zhou, Lihua Little, Peter Quirion, Remi Zheng, Wenhua affil: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and Neurophamacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510060 People's Republic of China sug: ab: Rationale: Lithium is currently used in the treatment of mental illness. We have previously reported that lithium stimulated the protein kinase B/Forkhead box O1 (Akt/FoxO1) pathway in rats. However, little information is available regarding its neuroprotective role of this pathway and underlying mechanisms. Objectives: PC12 cells treated with serum deprivation were used as a toxicity model to study the protective effect of lithium and its underlying mechanisms. Methods: Cell viability was determined by methyl thiazolyl tetrazolium assay and Hoechst staining. FoxO1 subcellular location and its overexpression were used to study the underlying mechanisms. Various pathway inhibitors were used to investigate the possible pathways, while the phosphorylation of Akt and FoxO1 was analyzed by Western blot. Results: Lithium pretreatment dose-dependently reduced PC12 cell apoptosis induced by serum starvation. The protective effect of lithium was abolished by LY294002, a PI3K-specific inhibitor, and Akt inhibitor Akt inhibitor VIII, whereas mitogen-activated protein kinase kinase (MEK kinase) inhibitor U0126 had no effect. Lithium induced the phosphorylation of Akt and FoxO1 in a time- and concentration-dependent manner. Lithium-induced phosphorylation of Akt and FoxO1 is mediated by the PI3K/Akt pathway. Serum deprivation caused nuclear translocation of FoxO1 while application of lithium reversed the effect of serum deprivation. Moreover, overexpression of FoxO1 enhanced cell apoptosis induced by serum withdrawal. Finally, lithium was found to reduce the exogenous and endogenous FoxO1 protein levels in PC12 cells in a concentration-dependent fashion. Conclusions: The protective effect of lithium against serum starvation cell death is mediated by the PI3K/Akt/FoxO1 pathway. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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