Insensitivity of PI3K/Akt/GSK3 signaling in peripheral blood mononuclear cells of age-related macular degeneration patients
Xunxian Liu
Zemin Yao
摘要：Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC),a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD),was associated with altered activation of phosphatidylinositide 3-kinase (PI3K),Akt,andglycogen synthase kinase 3 (GSK3).We wondered whether or not altered PI3K,Akt,and GSK3 activities could bedetected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients.In the patients' PBMC,absent or reduced serine-phosphorylation of GSK3α or GSK3β was observed,which was accompanied with increased phosphorylation ofGSK3 substrates (e.g.CCAAT enhancer binding protein α,insulin receptor substrate 1,and TAU),indicative of enhanced GSK3 activation.In addition,decreased protein mass of PI3K85α and tyrosinephosphorylation of PI3K50α was present in PBMC of the AMD patients,suggesting impaired PI3K activation.Moreover,abnormally lowered molecular weight forms of Akt and GSK3 were detected in PBMC of the AMD patients.These data demonstrate that despite the presence of high levels of IL-17RC,Wnt-3a and vascular endothelial growth factor,the PI3K/Akt/GSK3 signaling pathway is insensitive to these stimuli in PBMC of the AMD patients.Thus,measurement of PI3K/Akt/GSK3 expression and activity in PBMC may serve as a surrogate biomarker for AMD.
机标关键词：macular degenerationmononuclear cellsperipheral bloodretinal pigment epitheliumendothelial growth factorsignaling pathwaymolecular weightbinding protein
分类号：R774.5(视网膜及视神经疾病)
资助基金：an operating grant (MOP 123279)
论文发表日期：2017-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 248-255 )
英文信息