IGF-1 signaling via the PI3K/Akt pathway confers neuroprotection in human retinal pigment epithelial cells exposed to sodium nitroprusside insult

Wang, Haitao, Liao, Sufen, Geng, Ruojun, Zheng, Yongxin, Liao, Rifang, Yan, Fengxia, Thrimawithana, Thilini, Little, Peter J., Feng, Zhong-Ping, Lazarovici, Philip and Zheng, Wenhua (2015) IGF-1 signaling via the PI3K/Akt pathway confers neuroprotection in human retinal pigment epithelial cells exposed to sodium nitroprusside insult. Journal of Molecular Neuroscience, 55 4: 931-940. doi:10.1007/s12031-014-0448-7


Author Wang, Haitao
Liao, Sufen
Geng, Ruojun
Zheng, Yongxin
Liao, Rifang
Yan, Fengxia
Thrimawithana, Thilini
Little, Peter J.
Feng, Zhong-Ping
Lazarovici, Philip
Zheng, Wenhua
Title IGF-1 signaling via the PI3K/Akt pathway confers neuroprotection in human retinal pigment epithelial cells exposed to sodium nitroprusside insult
Journal name Journal of Molecular Neuroscience   Check publisher's open access policy
ISSN 1559-1166
0895-8696
Publication date 2015-04-01
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s12031-014-0448-7
Volume 55
Issue 4
Start page 931
End page 940
Total pages 10
Place of publication Totowa, NJ United States
Publisher Humana Press
Language eng
Abstract 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.
Keyword Insulin-like growth factor-1
Retinal pigment epithelium
Nitric oxide
Apoptosis
Akt
MAP kinase
Protection
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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