期刊
CELLULAR SIGNALLING
卷 31, 期 -, 页码 31-40出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2016.12.009
关键词
Cyclin-dependent kinase 5; Podocyte; Diabetic nephropathy; Endoplasmic reticulum stress; Apoptosis
类别
资金
- National Natural Science Foundation of China [81400731]
- Natural Science Fundation of Hebei Province [H2013206139, H2015206257]
- Excellent Youth Science Fund of Department of Education of Hebei Province of China [YQ2013002]
- China Postdoctoral Science Foundation [2016M591403]
Endoplasmic reticulum (ER) stress has been reported to be associated with podocyte apoptosis in diabetic nephropathy, but the mechanism of ER signaling in podocyte apoptosis hasn't been fully understood. Our previous studies have demonstrated that Cyclin-dependent kinase 5 (Cdk5) was associated with podocyte apoptosis in diabetic nephropathy. The present study was designed to examine whether and how Cdk5 activity plays a role in ER stress induced podocyte apoptosis in diabetic nephropathy. The results showed that along with induction of Cdk5 and apoptosis, GRP78 and its two sensors as well as CHOP and cleaved caspase-12 were induced in high glucose treated podocytes. These responses were attenuated by treated salubrinal. The ER stress inducer, tunicamycin, also up-regulated the kinase activity and protein expression of Cdk5 in podocytes accompanied with the increasing of GRP78. On the other hand, Cdk5 phosphorylates MEKK1 at Ser280 in tunicamycin treated podocytes, and together, they increase the JNK phosphorylation. Moreover, disruption of this pathway can decrease the podocyte apoptosis induced by tunicamycin. Therefore, our study proved that Cdk5 may play an important role in ER stress induced podocyte apoptosis through MEKK1/JNK pathway in diabetic nephropathy. (C) 2017 Elsevier Inc. All rights reserved.
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