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Experimental Diabetes Research
Volume 2012 (2012), Article ID 137607, 8 pages
http://dx.doi.org/10.1155/2012/137607
Research Article

The Antioxidant 3H-1,2-Dithiole-3-Thione Potentiates Advanced Glycation End-Product-Induced Oxidative Stress in SH-SY5Y Cells

1Department of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA
2The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA

Received 6 September 2011; Revised 24 February 2012; Accepted 26 February 2012

Academic Editor: N. Cameron

Copyright © 2012 Robert Pazdro and John R. Burgess. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oxidative stress is implicated as a major factor in the development of diabetes complications and is caused in part by advanced glycation end products (AGEs). AGEs ligate to the receptor for AGEs (RAGE), promoting protein kinase C (PKC)-dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide radical generation. While scavenging antioxidants are protective against AGEs, it is unknown if induction of endogenous antioxidant defenses has the same effect. In this study, we confirmed that the compound 3H-1,2-dithiole-3-thione (D3T) increases reduced-state glutathione (GSH) concentrations and NADPH:quinone oxidoreductase 1 (NQO1) activity in SH-SY5Y cells and provides protection against H2O2. Surprisingly, D3T potentiated oxidative damage caused by AGEs. In comparison to vehicle controls, D3T caused greater AGE-induced cytotoxicity and depletion of intracellular GSH levels while offering no protection against neurite degeneration or protein carbonylation. D3T potentiated AGE-induced reactive oxygen species (ROS) formation, an effect abrogated by inhibitors of PKC and NADPH oxidase. This study suggests that chemical induction of endogenous antioxidant defenses requires further examination in models of diabetes.