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Updated: May 17, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Proteomic analysis of protease resistant proteins in the diabetic rat kidney
Sneha B Bansode1, Ashok D Chougale, Rakesh S Joshi
1Proteomics Facility, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune-411008, India.
Abstract:
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.
Insights
Protein aggregates form due to advanced glycation end product modification, leading to impaired kidney function in diabetes. This aggregation results from reduced proteasomal activity and resistance to protein breakdown.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Protein aggregation is linked to diabetic complications and neurodegenerative diseases.
- Advanced glycation end products (AGEs) modify proteins, increasing their resistance to degradation.
- Impaired protein quality control mechanisms contribute to disease pathogenesis.
Purpose of the Study:
- To identify and characterize protease-resistant proteins in diabetic rat kidneys.
- To investigate the role of advanced glycation end products (AGEs) modification and ubiquitination in protein aggregation.
- To assess proteasomal activity and its impact on protein homeostasis in diabetic kidneys.
Main Methods:
- Streptozotocin-induced diabetic rat model.
- Protease resistance assays.
- Immunological and mass spectrometry analysis for AGEs modification and ubiquitination.
- Proteasomal activity assays.
- In silico prediction of aggregation-prone regions.
Main Results:
- Identified protease-resistant proteins involved in glucose metabolism and stress response in diabetic rat kidneys.
- Confirmed AGEs modification and ubiquitination of these resistant proteins.
- Demonstrated significantly impaired proteasomal activity in diabetic rat kidneys.
- Observed reduced functional activity of identified enzymes, compensated by enhanced gene expression.
- In silico analysis revealed correlation between aggregation-prone regions and AGEs modification sites.
Conclusions:
- Accumulation of protein aggregates in diabetic kidneys is driven by AGEs modification and protease resistance.
- Impaired proteasomal activity contributes significantly to the formation of these aggregates.
- AGEs modification and subsequent protein aggregation represent a critical mechanism in diabetic complications.
