山梨医科学雑誌　第19巻4号　107-116(2004)

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

Ikuno SHIMA, Hideo SHINDO, Takehiro SAITO, Jing CHEN, Atsushi SUGIYAMA, Masato TAWATA, Toshimasa ONAYA and Tetsuro KOBAYASHI

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.

Key words: diabetic neuropathy, mitochondrial dysfunction, oxidative stress, reactive oxygen species, apoptosis



本文は、編集委員会の意向によりインターネットには公開しておりません。図書館等でご覧ください。

Texts are not availavle on Internet.
目次・Contentsに戻る