Modulation of glutathione peroxidase activity by age-dependent carbonylation in glomeruli of diabetic mice

Aims Low levels of reactive oxygen species and resulting oxidative protein modifications may play a beneficial role in cellular function under stress conditions. Here we studied the influence of age-dependent protein carbonylation on expression and activity of the anti-oxidative selenoenzyme glutathione peroxidase (GPx) in insulin-deficient Ins2Akita mice and type 2 diabetic obese db/db mice in context of diabetic nephropathy. Methods Protein carbonylation, GPx expression and activity were examined in kidney tissue and lysates by common histological and protein biochemical methods. Results In kidneys of Ins2Akita mice, carbonylated proteins, GPx-1 and GPx-4 expression were mainly detected in podocytes and mesangial cells. GPx activity was increased in kidney cortex homogenates of these mice. Remarkably, young animals did not show a concomitant increase in GPx expression but enhanced GPx carbonylation. No carbonylation-dependent modification of GPx activity was detected in db/db mice. In cultured podocytes hyperglycemia induced an increase in GPx expression but had no effect on activity or carbonylation. In kidney tissue sections of type 1 or type 2 diabetes patients, GPx-1 and GPx-4 expression but not overall protein carbonylation was significantly decreased. Conclusions These results indicate the existence of a threshold for beneficial carbonylation-dependent redox signaling during the progression of diabetic nephropathy.