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IGF-1 Signaling via the PI3K/Akt Pathway Confers Neuroprotection in Human Retinal Pigment Epithelial Cells Exposed to Sodium Nitroprusside Insult
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  • 作者:Haitao Wang (1)
    Sufen Liao (1)
    Ruojun Geng (1)
    Yongxin Zheng (1)
    Rifang Liao (1)
    Fengxia Yan (1)
    Thilini Thrimawithana (2)
    Peter J. Little (2)
    Zhong-Ping Feng (3)
    Philip Lazarovici (4)
    Wenhua Zheng (1)

    1. State Key Laboratory of Ophthalmology
    ; Zhongshan Ophthalmic Center ; Sun Yat-sen University ; Guangzhou ; 510060 ; China
    2. Discipline of Pharmacy
    ; School of Medical Sciences and Diabetes Complications Group ; Health Innovations Research Institute ; RMIT University ; Bundoora ; Melbourne ; VIC ; 3083 ; Australia
    3. Department of Physiology
    ; Faculty of Medicine ; University of Toronto ; 1 King鈥檚 College Circle ; Toronto ; ON ; Canada ; M5S 1A8
    4. School of Pharmacy Institute for Drug Research
    ; Faculty of Medicine ; The Hebrew University of Jerusalem ; Jerusalem ; 91120 ; Israel
  • 关键词:Insulin ; like growth factor ; 1 ; Retinal pigment epithelium ; Nitric oxide ; Apoptosis ; Akt ; MAP kinase ; Protection
  • 刊名:Journal of Molecular Neuroscience
  • 出版年:2015
  • 出版时间:April 2015
  • 年:2015
  • 卷:55
  • 期:4
  • 页码:931-940
  • 全文大小:1,180 KB
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  • 刊物主题:Neurosciences; Neurochemistry; Cell Biology; Proteomics; Neurology;
  • 出版者:Springer US
  • ISSN:1559-1166
文摘
The pathological increase in the levels of the second messenger nitric oxide (NO) in the vitreous cavity and retina leads to injury and cell death of the retinal pigment epithelium (RPE) cells and eventually may contribute to the occurrence and development of diabetic retinopathy. In this study, we developed a cellular model of retinopathy using D407 cells (a human RPE cell line) exposed to sodium nitroprusside (SNP) and investigated the protective effect of the insulin-like growth factor-1 (IGF-1) towards this insult. Cell death and apoptosis were examined by the methyl thiazolyl tetrazolium assay and Hoechst staining, respectively. Specific inhibitors were used and phosphorylation of relevant signaling proteins was determined by Western blotting. SNP, in a concentration-dependent fashion, increased the production of reactive oxygen species (ROS) and lipid peroxidation process causing cell death by apoptosis of D407 cells. IGF-1, in a time- and dose-dependent manner, conferred protection towards SNP-mediated insult. Both phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) were activated by IGF-1 in relation to the protective effect. Blockade of the PI3K/Akt pathway abolished the protective effect of IGF-1 whereas inhibition of the MAPK pathway was ineffective. SNP decreased the phosphorylation of Akt in the cells while IGF-1 reversed this inhibitory effect. These results indicate that the protective effect of IGF-1 on D407 exposed to SNP insult is mediated by the PI3K/Akt pathway. This proposal may be exploited in the clinic to improve the viability of insulted retinal cells for maintaining physiological vision.

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