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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 |
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| cites | cdi_FETCH-LOGICAL-c451t-8aac2f228cf09ff91a148b0a358d8b8d980ef00102ef42d299350b0f1eb952dd3 |
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| container_title | Biochemical and biophysical research communications |
| container_volume | 366 |
| creator | Goto, Hideo Nishikawa, Takeshi Sonoda, Kazuhiro Kondo, Tatsuya Kukidome, Daisuke Fujisawa, Kazuo Yamashiro, Takeshi Motoshima, Hiroyuki Matsumura, Takeshi Tsuruzoe, Kaku Araki, Eiichi |
| description | 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. |
| doi_str_mv | 10.1016/j.bbrc.2007.12.041 |
| format | article |
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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.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2007.12.041</identifier><identifier>PMID: 18083119</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Biochemical and biophysical research communications, 2008-02, Vol.366 (3), p.814-820</ispartof><rights>2007 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-8aac2f228cf09ff91a148b0a358d8b8d980ef00102ef42d299350b0f1eb952dd3</citedby><cites>FETCH-LOGICAL-c451t-8aac2f228cf09ff91a148b0a358d8b8d980ef00102ef42d299350b0f1eb952dd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18083119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goto, Hideo</creatorcontrib><creatorcontrib>Nishikawa, Takeshi</creatorcontrib><creatorcontrib>Sonoda, Kazuhiro</creatorcontrib><creatorcontrib>Kondo, Tatsuya</creatorcontrib><creatorcontrib>Kukidome, Daisuke</creatorcontrib><creatorcontrib>Fujisawa, Kazuo</creatorcontrib><creatorcontrib>Yamashiro, Takeshi</creatorcontrib><creatorcontrib>Motoshima, Hiroyuki</creatorcontrib><creatorcontrib>Matsumura, Takeshi</creatorcontrib><creatorcontrib>Tsuruzoe, Kaku</creatorcontrib><creatorcontrib>Araki, Eiichi</creatorcontrib><title>Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>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.</description><subject>Animals</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - chemically induced</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetic complications</subject><subject>Diabetic Retinopathy - chemically induced</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium</subject><subject>Manganese superoxide dismutase</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Retina - metabolism</subject><subject>Streptozocin</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Up-Regulation</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQhoMoWqt_wIPsyduuM-l2TcCLaP0ARfALbyGbTDBlu1uTbdF_b0oLevI0A_PMy8zD2BFCgYDV6bSo62AKDnBWIC-gxC02QJCQc4Rymw0AoMq5xPc9th_jFACxrOQu20MBYoQoB-xp0tqu_6DG6yZ7aJ8fr7JuSYG-5oFi9F2bpWZJbR-zQL1vE_U2ubnO_gC-zazXdZqabOYNHbAdp5tIh5s6ZK_Xk5fL2_z-8ebu8uI-N-UY-1xobbjjXBgH0jmJGktRgx6NhRW1sFIAuXQycHIlt1zK0RhqcEi1HHNrR0N2ss6dh-5zQbFXMx8NNY1uqVtExaGqsEyPDhlfgyZ0MQZyah78TIdvhaBWJtVUrUyqlUmFXCWTael4k76oZ2R_VzbqEnC-Bij9uPQUVDSeWkPWBzK9sp3_L_8H7NmE9Q</recordid><startdate>20080215</startdate><enddate>20080215</enddate><creator>Goto, Hideo</creator><creator>Nishikawa, Takeshi</creator><creator>Sonoda, Kazuhiro</creator><creator>Kondo, Tatsuya</creator><creator>Kukidome, Daisuke</creator><creator>Fujisawa, Kazuo</creator><creator>Yamashiro, Takeshi</creator><creator>Motoshima, Hiroyuki</creator><creator>Matsumura, Takeshi</creator><creator>Tsuruzoe, Kaku</creator><creator>Araki, Eiichi</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20080215</creationdate><title>Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice</title><author>Goto, Hideo ; Nishikawa, Takeshi ; Sonoda, Kazuhiro ; Kondo, Tatsuya ; Kukidome, Daisuke ; Fujisawa, Kazuo ; Yamashiro, Takeshi ; Motoshima, Hiroyuki ; Matsumura, Takeshi ; Tsuruzoe, Kaku ; Araki, Eiichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-8aac2f228cf09ff91a148b0a358d8b8d980ef00102ef42d299350b0f1eb952dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - chemically induced</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetic complications</topic><topic>Diabetic Retinopathy - chemically induced</topic><topic>Diabetic Retinopathy - metabolism</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelium</topic><topic>Manganese superoxide dismutase</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Retina - metabolism</topic><topic>Streptozocin</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Up-Regulation</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goto, Hideo</creatorcontrib><creatorcontrib>Nishikawa, Takeshi</creatorcontrib><creatorcontrib>Sonoda, Kazuhiro</creatorcontrib><creatorcontrib>Kondo, Tatsuya</creatorcontrib><creatorcontrib>Kukidome, Daisuke</creatorcontrib><creatorcontrib>Fujisawa, Kazuo</creatorcontrib><creatorcontrib>Yamashiro, Takeshi</creatorcontrib><creatorcontrib>Motoshima, Hiroyuki</creatorcontrib><creatorcontrib>Matsumura, Takeshi</creatorcontrib><creatorcontrib>Tsuruzoe, Kaku</creatorcontrib><creatorcontrib>Araki, Eiichi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goto, Hideo</au><au>Nishikawa, Takeshi</au><au>Sonoda, Kazuhiro</au><au>Kondo, Tatsuya</au><au>Kukidome, Daisuke</au><au>Fujisawa, Kazuo</au><au>Yamashiro, Takeshi</au><au>Motoshima, Hiroyuki</au><au>Matsumura, Takeshi</au><au>Tsuruzoe, Kaku</au><au>Araki, Eiichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2008-02-15</date><risdate>2008</risdate><volume>366</volume><issue>3</issue><spage>814</spage><epage>820</epage><pages>814-820</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18083119</pmid><doi>10.1016/j.bbrc.2007.12.041</doi><tpages>7</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2008-02, Vol.366 (3), p.814-820 |
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| 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 |
| title | Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice |
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