High glucose‐induced oxidative stress and mitochondrial dysfunction in neurons
- 1 November 2002
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 16 (13), 1738-1748
- https://doi.org/10.1096/fj.01-1027com
Abstract
The current study examines the association between glucose induction of reactive oxygen species (ROS), mitochondrial (Mt) depolarization, and programmed cell death in primary neurons. In primary dorsal root ganglion (DRG) neurons, 45 mM glucose rapidly induces a peak rise in ROS corresponding to a 50% increase in mean Mt size at 6 h (PP<0.001), which inhibit specific components of the Mt electron transfer chain. Similarly, MMD and caspase-3 activation are inhibited by 100 μM bongkrekic acid (an inhibitor of the adenosine nucleotide translocase ANT). These results indicate that mild increases in glucose induce ROS and Mt swelling that precedes neuronal apoptosis. Glucotoxicity is blocked by inhibiting ROS induction, MMD, or caspase cleavage by specific inhibitors of electron transfer, or by stabilizing the ANT.—Russell, J. W., Golovoy, D., Vincent, A. M., Mahendru, P., Olzmann, J. A., Mentzer, A., Feldman, E. L. High glucose-induced oxidative stress and mitochondrial dysfunction in neurons.Keywords
Funding Information
- National Institutes of Health (NS01938, NS42056)
- U.S. Department of Veterans Affairs (NIH NS36778, NIH NS38849)
- Juvenile Diabetes Research Foundation International
- National Institute of Diabetes and Digestive and Kidney Diseases (#5P60DK-20572)
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