Thioredoxin interacting protein is increased in sensory neurons in experimental diabetes
- 作者：Sally A. Price ; Natalie J. Gardiner ; Beatriz Duran-Jimenez ; Leo A.H. Zeef ; Irina G. Obrosova and David R. Tomlinson
- 关键词：Diabetic neuropathy ; Thioredoxin interacting protein ; Vitamin D-upregulated protein 1 ; Microarray ; p38 MAP kinase ; Antioxidant
- 刊名：Brain Research
- 出版年：2006
- 期刊代码：8_00068993
- 类别：neu
- 出版时间：20 October 2006
- 卷：1116
- 期：1
- 页码：206-214
- 文件大小：841 K
摘要
Diabetic neuropathy is a major complication of diabetes and has multifactoral aetiology. The exact cause of damage is unknown although high glucose and oxidative stress are known to contribute significantly. In order to identify molecular targets of the disease and possibly new therapeutic targets, we previously examined the effect of diabetes on dorsal root ganglia (DRG) neurons using Affymetrix gene chip arrays. A number of individual genes and groups of genes were found to be dysregulated; the most significant of these was thioredoxin interacting protein (Txnip). This gene was found to have increased expression in DRG from diabetic rats with all durations of diabetes examined, including those that preceded the onset of functional changes such as decreased nerve conduction velocity. Increased Txnip expression therefore represents an early change in diabetic neuropathy that could, at least in part, be responsible for causing the initial functional deficits. This study confirmed the changes in Txnip expression at the mRNA and protein levels and identified the cell types responsible for the change. Furthermore we investigated the mechanism of diabetes-induced Txnip gene induction. Neither the antioxidant dexlipotam (R-lipoic acid) nor the p38 MAP kinase inhibitor SB239063 could prevent increases in Txnip expression despite reducing oxidative stress. However, treatment of rats with insulin prevented diabetes-induced increases in Txnip gene expression. These results indicate another mechanism by which diabetes may cause oxidative damage in peripheral nerve, and may represent a novel target for therapeutic intervention.