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Cyclin-dependent kinase 5 contributes to endoplasmic reticulum stress induced podocyte apoptosis via promoting MEKK1 phosphorylation at Ser280 in diabetic nephropathy.
- Source :
-
Cellular signalling [Cell Signal] 2017 Feb; Vol. 31, pp. 31-40. Date of Electronic Publication: 2016 Dec 24. - Publication Year :
- 2017
-
Abstract
- 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Cinnamates pharmacology
Endoplasmic Reticulum Chaperone BiP
Glucose toxicity
MAP Kinase Signaling System drug effects
Mice
Phosphorylation drug effects
Phosphoserine metabolism
Thiourea analogs & derivatives
Thiourea pharmacology
Tunicamycin pharmacology
Apoptosis drug effects
Cyclin-Dependent Kinase 5 metabolism
Diabetic Nephropathies enzymology
Diabetic Nephropathies pathology
Endoplasmic Reticulum Stress drug effects
MAP Kinase Kinase Kinase 1 metabolism
Podocytes pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3913
- Volume :
- 31
- Database :
- MEDLINE
- Journal :
- Cellular signalling
- Publication Type :
- Academic Journal
- Accession number :
- 28024901
- Full Text :
- https://doi.org/10.1016/j.cellsig.2016.12.009