Mechanism Research And Protective Effect Of Igfbp-rp1 On Oxidative Stress And Apoptosis Of Human Retinal Pigment Rpithelial

Purpose:To explore the protective effcet of insulin-like growth factor binding protein-related protein 1(IGFBP-rP1)against apoptosis induced by oxidative stress injury,and its underlying molecular mechanisms.Methods:Human RPE cells were incubated with different concerntrations of H2O2 for 24 h.Cell viability was measured by MTS assay.Apoptosis rates were detected using flow cytometry assay.Western bolt was used to detect the expression of IGFBP-rP1 in different group.Human RPE cells under oxidative stress were incubated with different concerntrations fo IGFBP-rP1(50ng/mL,100 ng/mL,200 ng/mL).Apoptosis rates were detected using flow cytometry assay and TUNEL assay.The expression of Caspase-9,P-Akt and P-ERK protein were assessed by Western blot.Results:When the concertration of H2O2 exceed 400 μmol/L,there are significant difference in cell viability and apoptotic rates between oxidative stress group and control group(P<0.001).The expression of IGFBP-rP1 protein in oxidative stress group was decreased significantly,campared with control group(P<0.001).Moreover,there was no significant difference in cell viability of RPE cells incubated with different conerntrations of IGFBP-rP1(P>0.05).The apoptotic rates and the expression of caspase-9 significant decreased in IGFBP-rP1 incubating group,caopared with the oxidative stress group(P<0.001),following the upregulation of P-Akt(P<0.001)and P-ERK(P<0.001)protein expression in a dose-dependent manner.Conclusions:IGFBP-rP1 protects RPE cells against apoptosis induced by oxidative stress by means of activating ERK and PI3K-Akt signaling pathway and down-regulating caspase-9 expression.It highlights the potential importance of IGFBP-rPl serving as a target of gene therapy for retinal degeneration in the future.