Role for nitrosative stress in diabetic neuropathy: evidence from studies with a peroxynitrite decomposition catalyst

Abstract
SPECIFIC AIMSDiabetic distal symmetric sensorimotor polyneuropathy affects up to 60–70% of patients with diabetes mellitus in the U.S. The best-studied mechanisms of diabetic neuropathy include increased aldose reductase (AR) activity, nonenzymatic glycation/glycooxidation, activation of protein kinase C, and impaired neurotrophic support. These mechanisms contribute to enhanced oxidative stress resulting from increased production of reactive oxygen species (ROS) and insufficient up- or down-regulation of antioxidative defense.Increased formation of the potent oxidant peroxynitrite (the product of superoxide anion radical reaction with nitric oxide) has been documented in experimental and clinical diabetic neuropathy. Peroxynitrite causes nitration and nitrosylation of biomolecules including proteins, lipids, and DNA. Nitrosative stress has been implicated in DNA single strand breakage, followed by poly(ADP-ribose) polymerase (PARP) activation, in pathological conditions associated with oxidative stress. ...
Funding Information
  • National Institutes of Health (DK59809-01, HL/DK 71215-01)