<Original Article> Effect of High Glucose Concentration on Mitochondrial Metabolism in Neuronal Cells

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<Original Article> Effect of High Glucose Concentration on Mitochondrial Metabolism in Neuronal Cells

Authors
Publisher
山梨大学医学会
Keywords
  • Apoptosis
  • Reactive Oxygen Species
  • Oxidative Stress
  • Diabetic Neuropathy
  • Mitochondrial Dysfunction

Abstract

Mitochondrial dysfunction caused by elevated extracellular glucose may play an important role in the pathogenesis of diabetic neuropathy. In this study, we investigated the effect of high glucose both on the mitochondrial respiratory chain and on the energy production in SH-SY5Y neruroblastoma cells, a model of peripheral neurons. We first measured total oxygen consumption rate of the cells cultured in various glucose concentrations using a polarographic method. We then mea sured the activity of each respiratory chain complex of the mitochondrial fractions of the cells cultured in either normal or high glucose. Finally, we measured the accumulation of the reactive oxygen species (ROS) in the cells. The total oxygen consumption of cells in high glucose concentration decreased in a dose- and time-dependent manner. Inhibitors of mitochondrial electron transport system reduced the oxygen consumption, while antioxidants improved it. We observed a significant decrease in the activity of respiratory chain complex I and complex III+IV of the cells in high glucose. We also observed an increase of ROS in the cells cultured in high glucose for more than 2 days. In conclusion, we propose that the impairment of the mitochondrial respiratory chain and the decrease in the energy production caused by oxidative stress in high glucose may be closely related to the pathogenesis of diabetic neuropathy.

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