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Updated: May 5, 2026

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Alterations of the kidney cortex proteome in response to exercise training in normoglycemic and hyperglycemic
Roger de Moraes, Richard H Valente, Ileana R Leon
1Laboratorio de Investigacao Cardiovascular, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365 - Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. etibi@ioc.fiocruz.br.
Abstract:
Hyperglycemia induces systemic vascular endothelial dysfunction and renal damage through the overproduction of reactive oxygen species (ROS). Regular aerobic exercise decreases the incidence of ROS-associated diseases and is involved in protection against systemic and renal vascular alterations. To investigate the impact of exercise training on renal protein expression in hyperglycemic conditions, we performed gel-based proteomic analyses of the rabbit kidney cortex from sedentary and exercised rabbits after exposure to normal or high glucose concentrations. Abundance of proteins in the renal cortex was determined by two-dimensional polyacrylamide gel electrophoresis followed by protein identification with mass spectrometry, using peptide mass and fragment fingerprintings. We identified the differential abundance of twenty seven proteins in exercise trained animals among the total of 324 spots, from which five proteins are related to the down-regulation of cellular oxidative stress (albumin, protein disulfide isomerase, heat shock protein 60-like chaperonin, DJ-1 and ubiquinol-cytochrome-c reductase), and three proteins are involved in energy metabolism (shortchain acyl-coenzyme A dehydrogenase, malate dehydrogenase and L-arginine-glycine amidinotransferase). We concluded that exercise training induces an increase in the abundance of five antioxidant proteins in the renal cortex, which could explain the well-known increase in endothelial-dependent vasodilation that results from exercise and the consequential protective effect against increased oxidative stress of the hyperglycemic milieu. Moreover, this protective effect could be important in the prevention of kidney vascular damage associated with diabetes pathophysiology.
Insights
Regular aerobic exercise boosts antioxidant proteins in the kidney cortex, protecting against hyperglycemia-induced oxidative stress and potential kidney damage. This finding highlights exercise
Area of Science:
- Proteomics
- Renal Physiology
- Oxidative Stress Biology
Background:
- Hyperglycemia causes oxidative stress, leading to vascular dysfunction and kidney damage.
- Aerobic exercise is known to reduce reactive oxygen species (ROS) and protect against vascular alterations.
Purpose of the Study:
- To investigate the effects of exercise training on renal protein expression in hyperglycemic rabbits.
- To identify specific proteins modulated by exercise that may confer protection against hyperglycemia.
Main Methods:
- Gel-based proteomic analysis of rabbit kidney cortex.
- Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry for protein identification.
- Comparison between sedentary and exercised rabbits under normal and high glucose conditions.
Main Results:
- Exercise training altered the abundance of 27 proteins in the renal cortex.
- Five proteins related to antioxidant defense (e.g., albumin, DJ-1) were upregulated by exercise.
- Three proteins involved in energy metabolism were also differentially abundant.
Conclusions:
- Exercise training increases antioxidant protein levels in the renal cortex, potentially mitigating hyperglycemia-induced oxidative stress.
- This exercise-induced antioxidant effect may explain improved endothelial function and protection against kidney vascular damage.
- Findings suggest exercise is a valuable strategy for preventing diabetic kidney disease pathophysiology.
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