Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice

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/en...

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Published in:Biochemical and biophysical research communications 2008-02, Vol.366 (3), p.814-820
Main Authors: Goto, Hideo, Nishikawa, Takeshi, Sonoda, Kazuhiro, Kondo, Tatsuya, Kukidome, Daisuke, Fujisawa, Kazuo, Yamashiro, Takeshi, Motoshima, Hiroyuki, Matsumura, Takeshi, Tsuruzoe, Kaku, Araki, Eiichi
Format: Article
Language:English
Subjects:
Animals
Diabetes
Diabetes Mellitus, Experimental - chemically induced
Diabetes Mellitus, Experimental - metabolism
Diabetic complications
Diabetic Retinopathy - chemically induced
Diabetic Retinopathy - metabolism
Endothelial Cells - metabolism
Endothelium
Manganese superoxide dismutase
Mice
Mice, Inbred C57BL
Mice, Transgenic
Reactive oxygen species
Reactive Oxygen Species - metabolism
Retina - metabolism
Streptozocin
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
Up-Regulation
Vascular Endothelial Growth Factor A - metabolism
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.12.041