title: Thiol-related genes in diabetic complications: a novel protective role for endogenous thioredoxin 2.
abstract: OBJECTIVE
  Our laboratory and others have found that deficiencies in cellular thiols may be importantly involved in the development of diabetic complications. However, the role for specific thiol-related genes in diabetic complications is unclear.
  
  
  RESULTS
  We began the present study by systematically determining the expression level of 11 thiol-related genes in three tissues from rats with streptozotocin-induced diabetes. Several thiol-related genes were found to exhibit diabetes-associated, time-dependent differential expression. Thioredoxin 2, a mitochondrion-specific thioredoxin whose role in diabetes was unknown, was suppressed in the aorta from rats with two weeks of diabetes. When thioredoxin 2 expression in human umbilical vein endothelial cells was knocked-down by small interfering RNA, high-ambient glucose-elicited substantial injurious effects (n=5 to 9, P<0.05), including increases in cytosolic cytochrome c (by 2.2+/-0.6-fold), lipid peroxidation (by 40+/-8%), fibronectin expression (by 35+/-7%), and oxidized glutathione, and decreases in endothelial nitric oxide synthase expression (by 79+/-15%), basal accumulation of nitrite/nitrate (by 68+/-16%), total free thiols (by 42+/-8%), and glutathione (by 6+/-1%). In the absence of thioredoxin 2 knockdown, high-ambient glucose did not have significant effects on any of these measurements. The effect of thioredoxin 2 knockdown appeared to be associated with increases in glucose consumption and glucose transporter 1 expression.
  
  
  CONCLUSIONS
  These results provided the first expression profile of thiol-related genes in a model of diabetes and demonstrated a novel role for endogenous thioredoxin 2 in protecting cells against high ambient glucose.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. mliang@mcw.edu
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pietrusz
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D048909:Diabetes Complications / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000502:physiology*; D013879:Thioredoxins / Q000235:genetics*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
chemical_list: D005353:Fibronectins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D013438:Sulfhydryl Compounds; C516113:Txn2 protein, rat; D009569:Nitric Oxide; D013879:Thioredoxins; D045304:Cytochromes c; D005947:Glucose