Abstract
Diabetic neuropathy is a common diabetic complication. Oxidative stress (OS) is a significant mediator in the development of diabetic neuropathy. Exposing neurons to hyperglycaemia increases OS, inhibits neurite out-growth and causes apoptosis. In the present study we explore the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase vs. mitochondrial reactive oxygen species (mtROS) in diabetic neuropathy. Human neuroblastoma SH-SY5Y cells were treated with high glucose (25 mM) or normal glucose (5.5 mM) in the presence and absence of the specific NADPH oxidase inhibitor gp91ds-tat (6 days). Caspase activity, intracellular ROS, mtROS production, mitochondrial membrane potential (ΔYm) and NADPH oxidase activity were measured. Neurite outgrowth and neurites/cell were analysed using Image J software. Chronic exposure to high glucose increased caspases activity and cytoplasmic but not mtROS levels, and reduced the number of neurites/cell and the neurite outgrowth compared to normal glucose. Co-treatment with gp91ds-tat reversed the increased levels of ROS and prevented glucose-induced neurite inhibition. ΔYm and mtROS levels were unaffected at the end of the treatment. The current study demonstrates that NADPH oxidase, and not the mitochondria derived ROS, is responsible for the induction of apoptosis in SH-SY5Y cells. The use of NADPH oxidase inhibitors may prove to be of therapeutic value in the treatment of diabetic neuropathy.
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