Proteomic Analysis of Protease Resistant Proteins in the Diabetic Rat Kidney

Glycation induced protein aggregation has been implicated in the development of diabetic complications and neurodegenerative diseases. These aggregates are known to be resistant to proteolytic digestion. Here we report the identification of protease resistant proteins from the streptozotocin induced...

Full description

Saved in:
Bibliographic Details
Published in:Molecular & cellular proteomics 2013-01, Vol.12 (1), p.228-236
Main Authors: Bansode, Sneha B., Chougale, Ashok D., Joshi, Rakesh S., Giri, Ashok P., Bodhankar, Subhash L., Harsulkar, Abhay M., Kulkarni, Mahesh J.
Format: Article
Language:English
Subjects:
Animals
Diabetes Mellitus, Experimental - metabolism
Glucose - metabolism
Glycation End Products, Advanced - metabolism
Kidney - metabolism
Male
Peptide Hydrolases - metabolism
Proteasome Endopeptidase Complex - metabolism
Proteome - analysis
Proteomics
Rats
Rats, Wistar
Streptozocin
Stress, Physiological
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glycation induced protein aggregation has been implicated in the development of diabetic complications and neurodegenerative diseases. These aggregates are known to be resistant to proteolytic digestion. Here we report the identification of protease resistant proteins from the streptozotocin induced diabetic rat kidney, which included enzymes in glucose metabolism and stress response proteins. These protease resistant proteins were characterized to be advanced glycation end products modified and ubiquitinated by immunological and mass spectrometry analysis. Further, diabetic rat kidney exhibited significantly impaired proteasomal activity. The functional analysis of identified physiologically important enzymes showed that their activity was reduced in diabetic condition. Loss of functional activity of these proteins was compensated by enhanced gene expression. Aggregation prone regions were predicted by in silico analysis and compared with advanced glycation end products modification sites. These findings suggested that the accumulation of protein aggregates is an inevitable consequence of impaired proteasomal activity and protease resistance due to advanced glycation end products modification.
ISSN:1535-9476
1535-9484
DOI:10.1074/mcp.M112.020651