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Amiodarone-Induced Retinal Neuronal Cell Apoptosis Attenuated by IGF-1 via Counter Regulation of the PI3k/Akt/FoxO3a Pathway
Liao, Rifang1,2; Yan, Fengxia1,2; Zeng, Zhuanping3; Farhan, Mohd2; Little, Peter4; Quirion, Remi5; Srivastava, Lalit K.5; Zheng, Wenhua1,2
2017-11
Source PublicationMOLECULAR NEUROBIOLOGY
ISSN0893-7648
Volume54Issue:9Pages:6931-6943
Abstract

Amiodarone (AM) is the most effective antiarrhythmic agent currently available. However, clinical application of AM is limited by its serious toxic adverse effects including optic neuropathy. The purpose of this study was to explore the effects of AM and to assess if insulin-like growth factor-1 (IGF-1) could protect retinal neuronal cells from AM-induced apoptosis, and to determine the molecular mechanisms underlying the effects. Accordingly, the phosphorylation/activation of Akt and FoxO3a were analyzed by Western blot while the possible pathways involved in the protection of IGF-1 were investigated by application of various pathway inhibitors. The full electroretinogram (FERG) was used to evaluate in vivo effect of AM and IGF-1 on rat retinal physiological functions. Our results showed that AM concentration dependently caused an apoptosis of RGC-5 cells, while IGF-1 protected RGC-5 cells against this effect by AM. The protective effect of IGF-1 was reversed by PI3K inhibitors LY294002 and wortmannin as well as the Akt inhibitor VIII. AM decreased p-Akt and p-FoxO3a while increased the nuclear localization of FoxO3a in the RGC-5 cells. IGF-1 reversed the effect of AM on the p-Akt and p-FoxO3a and the nuclear translocation of FoxO3a. Similar results were obtained in primary cultured retinal ganglia cells. Furthermore, FERG in vivo recording in rats showed that AM decreased a-wave and b-wave of FERG while IGF-1 reversed the effects of AM. These data show that AM induced apoptosis of retinal neuronal cells via inhibiting the PI3K/Akt/FoxO3a pathway while IGF-1 protected RGC-5 cells against AM-induced cell apoptosis by stimulating this pathway.

KeywordAmiodarone Foxo3a Akt Antiarrhythmic Apoptosis Neuroprotection
DOI10.1007/s12035-016-0211-x
URLView the original
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000412030500023
PublisherHUMANA PRESS INC
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Neuropharmacology, School of Pharmaceutical Sciences, and Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
2.Faculty of Health Sciences, University of Macau, Macau, China
3.School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510006, China
4.School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE), The University of Queensland, 20 Cornwall St, Woolloongabba, QLD 4102, Australia
5.Douglas Hospital Research Center, McGill University, Montreal, QC, Canada
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Liao, Rifang,Yan, Fengxia,Zeng, Zhuanping,et al. Amiodarone-Induced Retinal Neuronal Cell Apoptosis Attenuated by IGF-1 via Counter Regulation of the PI3k/Akt/FoxO3a Pathway[J]. MOLECULAR NEUROBIOLOGY,2017,54(9):6931-6943.
APA Liao, Rifang.,Yan, Fengxia.,Zeng, Zhuanping.,Farhan, Mohd.,Little, Peter.,...&Zheng, Wenhua.(2017).Amiodarone-Induced Retinal Neuronal Cell Apoptosis Attenuated by IGF-1 via Counter Regulation of the PI3k/Akt/FoxO3a Pathway.MOLECULAR NEUROBIOLOGY,54(9),6931-6943.
MLA Liao, Rifang,et al."Amiodarone-Induced Retinal Neuronal Cell Apoptosis Attenuated by IGF-1 via Counter Regulation of the PI3k/Akt/FoxO3a Pathway".MOLECULAR NEUROBIOLOGY 54.9(2017):6931-6943.
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