Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid ...Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.展开更多
基金supported by the National Natural Science Foundation of China,No.U1304815a grant from Key Project of Science and Technology Research of Henan Province of China,No.132102310097
文摘Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.
文摘目的探讨FoxO1基因在新疆维吾尔族先天性马蹄内翻足(ICTEV)中的表达及FoxO1与先天性马蹄内翻足畸形程度的相关性。方法运用Western Blot方法检测新疆地区51例维吾尔族先天性马蹄内翻足患儿和25例维吾尔族健康儿童足部肌肉组织中FoxO1蛋白表达水平;应用实时荧光定量PCR测定不同畸形程度维吾尔族先天性马蹄内翻足患儿FoxO1mRNA相对表达量。结果 Western Blot检测结果显示ICTEV患儿FoxO1蛋白表达水平(0.52±0.23)低于正常儿童(1.61±0.15),两组比较差异有统计学意义(P=0.017)。实时荧光定量PCR检测显示,DimeglioⅡ、Ⅲ、Ⅳ型ICTEV的FoxO1mRNA相对表达量分别为1.02±0.24、0.67±0.15、0.24±0.19;维吾尔族ICTEV畸形程度与FoxO1mRNA相对表达量呈负相关性(P=0.039)。结论 FoxO1基因转录水平随ICTEV畸形程度的加重而逐渐降低,提示FoxO1基因可能参与了维吾尔族ICTEV的整个发病过程。
