Differential Effects of High Glucose and Methylglyoxal on Viability and Polyol Metabolism in Immortalized Adult Mouse Schwann Cells

Abstract

Cultured Schwann cells under exposure to high glucose and methylglyoxal (MG) have been individually employed for studying diabetic neuropathy; however, similarities and differences between these two culture models have not been studied. We investigated the effects of high glucose and MG on viability, polyol pathway activity, and expression of oxidative stress markers (4-hydroxy-2-nonenal (4HNE), acrolein (ACR), and hexanoyl lysine (HEL)) in immortalized adult mouse Schwann cells (IMS32 cell line) in culture. Western blot and immunocytochemical analyses revealed that expression of aldose reductase (AR), 4HNE, ACR, and HEL in IMS32 was induced by exposure to both high glucose (30 mM) and MG (0.5 mM) for 48 h. Treatment with MG (0.1, 0.2, and 0.5 mM) induced cell death in a concentrationdependent manner, whereas high glucose environments (30 mM and 56 mM) did not impair cell viability. In contrast, intracellular sorbitol and fructose levels were significantly increased by high glucose, but not by MG. Taking these findings together, IMS32 cell line under high glucose conditions appears to be useful for studying oxidative stress in relation to the polyol pathway hyperactivity in diabetes. MG is capable of causing more detrimental damage to IMS32 than high glucose, but MG-induced upregulation of AR is unlikely to accelerate the polyol pathway activity.