Effect of resveratrol pre-intervention on endoplasmic reticulum stress induced mouse podocyte apoptosis by using angiotensin II

Abstract

Objective To study the role of endoplasmic reticulum stress and c-Jun N-terminal kinase(JNK) pathway in angiotensin Ⅱ (Ang Ⅱ)-caused glomerular podocyte injury and the protection mechanism of resveratrol. Methods The mouse potocytes were induced differentiation and randomly divided into control group, high AngⅡ group and resveratrol intervention group (AngⅡ +Res group), and the specific inhibitor of JNK pathway SP600125 intervention group (Ang Ⅱ + SP600125 group). Control group was incubated with RPMI1640 medium, the AngⅡ concentration was 10-8 mol/L, resveratrol concentration was 20 μmol/L, SP600125 concentration was 20 μmol/L. Podocyte morphology in different groups was observed with inverted microscope after treated for 48 hours, and the apoptosis rate was measured with flow cytometer. The mRNA and protein expression of glucose regulated protein 78(GRP78) mRNA and phosphorylated JNK(p-JNK) was messured with real-time quantitative polymerase chain reaction(RT-PCR) and Western blotting. The t test was used for data analysis between group. Results Compared with those in the control group, the apoptosis rate and mRNA expression of GRP78 and p-JNK increased significantly in the AngⅡ group(t=9.318, 6.063, 7.160,P<0.05), and the protein expression of GRP78 and p-JNK ascended significantly too(GRP78 protein and p-JNK protein Ⅰ strip, Ⅱ strip,t=4.116, 5.085, 5.117,P<0.05). Compared with those in Ang Ⅱ Group, the apoptosis rate and mRNA and protein expression of GRP78 decreased significantly in Ang Ⅱ + Res group(t=14.328, 4.530, 3.977,P<0.05), the mRNA and protein expression of p-JNK descended significantly too(mRNA and protein Ⅰ strip, Ⅱ strip,t=4.590, 4.990, 4.991, P<0.05). Compared with those in Ang Ⅱ group, apoptosis rate (t=10.756,P<0.05) and the mRNA and protein expression of p-JNK in SP600125 intervention group decreased significantly(mRNA and protein Ⅰ strip, Ⅱ strip,t=5.408, 4.901, 4.886,P<0.05). Conclusions Podocyte apoptosis can be induced by Ang Ⅱ in vitro, and it causes apoptosis through endoplasmic reticulum stress and JNK path. However, resveratrol inhibits the apoptosis through inhibition endoplasmic reticulum stress and activation of JNK pathway. Key words: Podocyte; Endoplasmic reticulum stress; Resveratrol; SP600125