Oxidative Stress Injury To PC12 Cells Under Glycating Conditions

Abstract

A major complication in diabetes is loss of peripheral nerve function, termed as diabetic neuropathy. Glycation of cellular proteins by reducing sugars contributes to neuronal death and loss of nerve function. Hyperglycemia present in diabetes leads to increased production of methylglyoxal (MG), a strong glycating agent, forming advanced glycation end products (AGEs). The accumulation of AGEs has been implicated in several long‐term diabetic complications. One of the mechanisms involved is oxidative stress. We used PC12 cells treated with MG to determine the mechanism(s) involved in apoptosis of cells under glycating conditions. MG at 0.8 mM caused 70% cell death. The effect was observed as early as 6 hours of treatment. Caspase activity was increased in treated cells, indicating that MG caused apoptosis of cells. Treatment with curcumin, a compound from turmeric known for its antioxidant properties, inhibited the effect of MG and 80% of treated cells remained viable. Treatment with glutathione showed a similar, although less effective protection (60% survival). These results suggested that MG may cause oxidative stress to cells. We are currently studying the expression of iNOS and glutathione metabolizing enzymes. Our studies suggest that restoring redox balance in the cell may be an effective way of reducing cell death observed under glycating conditions.