http://hdl.handle.net/2027.42/78395 Mon, 20 May 2013 12:55:20 GMT 2013-05-20T12:55:20Z http://deepblue.lib.umich.edu:80/bitstream/id/279985/216680.gif http://hdl.handle.net/2027.42/78395 http://hdl.handle.net/2027.42/78315 Literature-based discovery of diabetes- and ROS-related targets Hur, Junguk; Sullivan, Kelli A; Schuyler, Adam D; Hong, Yu; Pande, Manjusha; States, David J; Jagadish, H. V; Feldman, Eva L Abstract Background Reactive oxygen species (ROS) are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins) collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG) of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/). Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy. Wed, 27 Oct 2010 00:00:00 GMT http://hdl.handle.net/2027.42/78315 2010-10-27T00:00:00Z http://hdl.handle.net/2027.42/78129 Sensory Neurons and Schwann Cells Respond to Oxidative Stress by Increasing Antioxidant Defense Mechanisms Vincent, Andrea M.; Kato, Koichi; McLean, Lisa L.; Soules, Mary E.; Feldman, Eva L. Abstract Elevated blood glucose is a key initiator of mechanisms leading to diabetic neuropathy. Increases in glucose induce acute mitochondrial oxidative stress in dorsal root ganglion (DRG) neurons, the sensory neurons normally affected in diabetic neuropathy, whereas Schwann cells are largely unaffected. We propose that activation of an antioxidant response in DRG neurons would prevent glucose-induced injury. In this study, mild oxidative stress (1 μM H2O2) leads to the activation of the transcription factor Nrf2 and expression of antioxidant (phase II) enzymes. DRG neurons are thus protected from subsequent hyperglycemia-induced injury, as determined by activation of caspase 3 and the TUNEL assay. Schwann cells display high basal antioxidant enzyme expression and respond to hyperglycemia and mild oxidative stress via further increases in these enzymes. The botanical compounds resveratrol and sulforaphane activate the antioxidant response in DRG neurons. Other drugs that protect DRG neurons and block mitochondrial superoxide, identified in a compound screen, have differential ability to activate the antioxidant response. Multiple cellular targets exist for the prevention of hyperglycemic oxidative stress in DRG neurons, and these form the basis for new therapeutic strategies against diabetic neuropathy. Antioxid. Redox Signal. 11, 425-438. Sun, 01 Mar 2009 00:00:00 GMT http://hdl.handle.net/2027.42/78129 2009-03-01T00:00:00Z http://hdl.handle.net/2027.42/75524 Insulin-like Growth Factor Binding Protein Expression in SH-SY5Y Neuroblastoma Cells Feldman, Eva L.; Randolph, Ann; Yee, Douglas Sun, 01 Aug 1993 00:00:00 GMT http://hdl.handle.net/2027.42/75524 1993-08-01T00:00:00Z http://hdl.handle.net/2027.42/75362 The Aetiology of Diabetic Neuropathy: the Combined Roles of Metabolic and Vascular Defects Stevens, M. J.; Feldman, Eva L.; Greene, D. A. Sat, 01 Jul 1995 00:00:00 GMT http://hdl.handle.net/2027.42/75362 1995-07-01T00:00:00Z