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

作者：Wiedenmann Tanja; Dietrich Nadine; Fleming Thomas; Altamura Sandro; Deelman Leo E; Henning Rob H; Muckenthaler Martina U; Nawroth Peter P; Hammes Hans Peter; Wagner Andreas H^*; Hecker Markus

来源：Journal of Diabetes and Its Complications, 2018, 32(2): 130-138.

DOI：10.1016/j.jdiacomp.2017.11.007

• Diabetic nephropathy
• Protein carbonylation
• Reactive oxygen species
• Hyperglycemia
• Glutathione peroxidase
• Podocytes

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 Ins2(Akita) 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 Ins2(Akita) 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.

• 出版日期2018-2