雷帕霉素激活自噬改善嘌呤霉素氨基核苷诱导的足细胞损伤 |
| |
引用本文: | 詹慧芳,刘文娟,金娟,龚建光,赵黎,何强. 雷帕霉素激活自噬改善嘌呤霉素氨基核苷诱导的足细胞损伤[J]. 中国免疫学杂志, 2018, 34(2): 188 |
| |
作者姓名: | 詹慧芳 刘文娟 金娟 龚建光 赵黎 何强 |
| |
作者单位: | 浙江大学校医院紫金港校区;浙江省人民医院;杭州医学院附属人民医院; |
| |
摘 要: | 目的:通过观察雷帕霉素对PAN 诱导的足细胞损伤及自噬相关蛋白表达的影响,探讨自噬在雷帕霉素保护PAN 诱导的足细胞损伤中的作用及可能机制。方法:构建PAN 诱导的足细胞损伤模型,将足细胞分成对照组(Control 组),PAN 组(加入50 μg/ ml PAN),雷帕霉素组(RAP 组:分别加入100、200、300 ng/ ml 雷帕霉素),PAN+雷帕霉素组(PAN+RAP组:细胞在用含PAN 的培养液培养前1 h,分别用100、200、300 ng/ ml 雷帕霉素进行预处理1 h)。采用Annexin V/ PI 双染法检测细胞凋亡,透射电镜观察自噬小体,Western blot 检测LC3、p62、4EBP1、P70S6K、mTOR 蛋白表达。结果:与对照组比较,PAN组足细胞凋亡增加,自噬体减少,LC3域蛋白表达下调,p62 上调,mTOR、4EBP1、P70S6K 磷酸化水平上调;与PAN 组比较,PAN+RAP 组足细胞凋亡率下降,自噬体增加,LC3域蛋白表达上调,p62 下调,mTOR、4EBP1、P70S6K 磷酸化水平下调。结论:PAN 可以抑制足细胞自噬,促进足细胞凋亡;雷帕霉素可通过激活自噬改善PAN 诱导的足细胞损伤,这种作用可能与雷帕霉素抑制mTOR/4EBP1、P70S6K 信号通路有关。
|
关 键 词: | 雷帕霉素,嘌呤霉素氨基核苷,足细胞 自噬,mTOR 信号通路, |
Rapamycin protect puromycin amino nucleoside induced podocyte injury by up-regulating autophagy |
| |
Abstract: | Objective:To explore the protective effect of rapamycin and the role of autophagy on podocyte injury induced by pu-romycin amino nucleoside.Methods: The mice podocytes cell 5(MPC5)were randomly divided into four groups:Control group,PAN group(50 μg/ ml PAN);rapamycin group(RAP group,100 ng/ ml,200 ng/ ml,300 ng/ ml rapamycin) and PAN+rapamycin group(PAN+RAP group,treated with rapamycin before PAN).The apoptosis of podocytes were detected by Annexin V/ PI.Transmission electronic microscopy was used to observe the formation of autophagosome.The expression of autophagic markers,LC3,p62,and 4EBP1,P70S6K,mTOR were detected by Western blot.Results: The podocyte apoptotic rate was significantly decreased when the podocytes were treated with rapamycin compared with PAN group .Further,more autophagosomes appeared in cytoplasm of podocytes in RAP and PAN+RAP group compared with PAN group.And the expression of LC3Ⅱwas significantly increased in rapamycin treated podocytes,whereas the expression of p62 was decreased markedly.Phosphorylation of mTOR,4EBP1 and P70S6K was decreased rapamycin treated groups.Conclusion: Podocyte autophagy was inhibited by PAN, and the apoptosis of podocytes was promoted.Rapamycin protect puromycin amino nucleoside induced podocyte injury by upregulating autophagy and it may be concerned with mTOR 4EBP1 and P70S6K signaling pathway. |
| |
Keywords: | |
本文献已被 CNKI 等数据库收录! |
| 点击此处可从《中国免疫学杂志》浏览原始摘要信息 |
|
点击此处可从《中国免疫学杂志》下载全文 |
|