Oxidative stress and cellular stress response in diabetic nephropathy

Cell Stress Chaperones. Winter 2007;12(4):299-306. doi: 10.1379/csc-270.1.


Oxidative stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status, a cellular-adaptive response occurs requiring functional chaperones, antioxidant production, and protein degradation. This study was designed to evaluate systemic oxidative stress and cellular stress response in patients suffering from type 2 diabetes-induced nephropathy and in age-matched healthy subjects. Systemic oxidative stress has been evaluated by measuring advanced glycation end-products (pentosidine), protein oxidation (protein carbonyls [DNPH]), and lipid oxidation (4-hydroxy-2-nonenal [HNE] and F2-isoprostanes) in plasma, lymphocytes, and urine, whereas the lymphocyte levels of the heat shock proteins (Hsps) heme oxygenase-1 (HO-1), Hsp70, and Hsp60 as well as thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic cellular stress response. We found increased levels of pentosidine (P < 0.01), DNPH (P < 0.05 and P < 0.01), HNE (P < 0.05 and P < 0.01), and F2-isoprostanes (P < 0.01) in all the samples from type 2 diabetic patients with nephropathy with respect to control group. This was paralleled by a significant induction of cellular HO-1, Hsp60, Hsp70, and TrxR-1 (P < 0.05 and P < 0.01). A significant upregulation of both HO-1 and Hsp70 has been detected also in lymphocytes from type 2 diabetic patients without uraemia. Significant positive correlations between DNPH and Hsp60, as well as between the degree of renal failure and HO-1 or Hsp70, also have been found in diabetic uremic subjects. In conclusion, patients affected by type 2 diabetes complicated with nephropathy are under condition of systemic oxidative stress, and the induction of Hsp and TrxR-1 is a maintained response in counteracting the intracellular pro-oxidant status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / blood
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Arginine / urine
  • Chaperonin 60 / metabolism
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology*
  • F2-Isoprostanes / blood
  • F2-Isoprostanes / urine
  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Response
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Lymphocytes / metabolism
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Lysine / urine
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Protein Carbonylation
  • Renal Insufficiency / pathology
  • Thioredoxin Reductase 1 / metabolism


  • Aldehydes
  • Chaperonin 60
  • F2-Isoprostanes
  • HSP70 Heat-Shock Proteins
  • Arginine
  • pentosidine
  • Heme Oxygenase-1
  • Thioredoxin Reductase 1
  • 4-hydroxy-2-nonenal
  • Lysine