title: Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice.
abstract: We previously proposed that hyperglycemia-induced mitochondrial ROS overproduction is a key event in the development of diabetic complications. In this study, we established a novel transgenic mouse (eMnSOD-Tg), which specifically expressed MnSOD in endothelial cells, by employing a Tie2 promoter/enhancer, and investigated the impact of mitochondrial ROS production on diabetic retinopathy in vivo. Using immunohistochemistry, overexpression of MnSOD in endothelial cells was confirmed in eMnSOD-Tg mice. By introduction of diabetes by streptozotocin, levels of urinary 8-hydroxydeoxyguanosine, a marker of mitochondrial oxidative stress, and expression of VEGF mRNA and protein and fibronectin mRNA in retinas were increased in wild-type littermates. However, these observations were ameliorated in eMnSOD-Tg mice, although control and eMnSOD-Tg mice showed a comparable level of hyperglycemia. In the present study, we newly developed a line of transgenic mice, which specifically express MnSOD in endothelium. In addition, overexpression of mitochondrial-specific SOD in endothelium could prevent diabetic retinopathy in vivo.
authors: Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors: Hideo
authors: H
authors: Goto
authors: Takeshi
authors: T
authors: Nishikawa
authors: Kazuhiro
authors: K
authors: Sonoda
authors: Tatsuya
authors: T
authors: Kondo
authors: Daisuke
authors: D
authors: Kukidome
authors: Kazuo
authors: K
authors: Fujisawa
authors: Takeshi
authors: T
authors: Yamashiro
authors: Hiroyuki
authors: H
authors: Motoshima
authors: Takeshi
authors: T
authors: Matsumura
authors: Kaku
authors: K
authors: Tsuruzoe
authors: Eiichi
authors: E
authors: Araki
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin; D013482:Superoxide Dismutase