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Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways
Zeng Z.1,2; Wang H.3; Shang F.3; Zhou L.4; Little P.J.5; Quirion R.6; Zheng W.7
2016
Source PublicationPsychopharmacology
ISSN333158
Volume233Issue:5Pages:785
Abstract

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. © 2015 Springer-Verlag Berlin Heidelberg.

KeywordApoptosis Lithium Neuroprotection Pi3k/akt/foxo1 Serum Deprivation
DOI10.1007/s00213-015-4168-7
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS SubjectNeurosciences ; Pharmacology & Pharmacy ; Psychiatry
WOS IDWOS:000370272300006
The Source to ArticleScopus
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Faculty of Health Science, University of Macau, Room 4021, Building E12, Avenida de Universidade Taipa, Macau, People's Republic of China.
2.Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Collaborative Innovation Center for Neurogenetics and Channelopathies, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
3.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.
4.Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
5.School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia.
6.Douglas Hospital Research Center, McGill University, Montreal, Canada.
7.Faculty of Health Science, University of Macau, Room 4021, Building E12, Avenida de Universidade Taipa, Macau, People's Republic of China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Zeng Z.,Wang H.,Shang F.,et al. Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways[J]. Psychopharmacology,2016,233(5):785.
APA Zeng Z..,Wang H..,Shang F..,Zhou L..,Little P.J..,...&Zheng W..(2016).Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways.Psychopharmacology,233(5),785.
MLA Zeng Z.,et al."Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways".Psychopharmacology 233.5(2016):785.
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