尿酸诱导的内皮功能障碍与线粒体改变和细胞内ATP浓度降低有关。

Nephron Experimental Nephrology Pub Date : 2012-01-01 Epub Date: 2012-12-07 DOI:10.1159/000345509
Laura Gabriela Sánchez-Lozada, Miguel A Lanaspa, Magdalena Cristóbal-García, Fernando García-Arroyo, Virgilia Soto, David Cruz-Robles, Takahiko Nakagawa, Min A Yu, Duk-Hee Kang, Richard J Johnson
{"title":"尿酸诱导的内皮功能障碍与线粒体改变和细胞内ATP浓度降低有关。","authors":"Laura Gabriela Sánchez-Lozada,&nbsp;Miguel A Lanaspa,&nbsp;Magdalena Cristóbal-García,&nbsp;Fernando García-Arroyo,&nbsp;Virgilia Soto,&nbsp;David Cruz-Robles,&nbsp;Takahiko Nakagawa,&nbsp;Min A Yu,&nbsp;Duk-Hee Kang,&nbsp;Richard J Johnson","doi":"10.1159/000345509","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aims: </strong>Endothelial dysfunction is associated with mitochondrial alterations. We hypothesized that uric acid (UA), which can induce endothelial dysfunction in vitro and in vivo, might also alter mitochondrial function.</p><p><strong>Methods: </strong>Human aortic endothelial cells were exposed to soluble UA and measurements of oxidative stress, nitric oxide, mitochondrial density, ATP production, aconitase-2 and enoyl Co-A hydratase-1 expressions, and aconitase-2 activity in isolated mitochondria were determined. The effect of hyperuricemia induced by uricase inhibition in rats on renal mitochondrial integrity was also assessed.</p><p><strong>Results: </strong>UA-induced endothelial dysfunction was associated with reduced mitochondrial mass and ATP production. UA also decreased aconitase-2 activity and lowered enoyl CoA hydratase-1 expression. Hyperuricemic rats showed increased mitDNA damage in association with higher levels of intrarenal UA and oxidative stress.</p><p><strong>Conclusions: </strong>UA-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP. These studies provide additional evidence for a deleterious effect of UA on vascular function that could be important in the pathogenesis of hypertension and vascular disease.</p>","PeriodicalId":18993,"journal":{"name":"Nephron Experimental Nephrology","volume":"121 3-4","pages":"e71-8"},"PeriodicalIF":0.0000,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000345509","citationCount":"242","resultStr":"{\"title\":\"Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations.\",\"authors\":\"Laura Gabriela Sánchez-Lozada,&nbsp;Miguel A Lanaspa,&nbsp;Magdalena Cristóbal-García,&nbsp;Fernando García-Arroyo,&nbsp;Virgilia Soto,&nbsp;David Cruz-Robles,&nbsp;Takahiko Nakagawa,&nbsp;Min A Yu,&nbsp;Duk-Hee Kang,&nbsp;Richard J Johnson\",\"doi\":\"10.1159/000345509\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aims: </strong>Endothelial dysfunction is associated with mitochondrial alterations. We hypothesized that uric acid (UA), which can induce endothelial dysfunction in vitro and in vivo, might also alter mitochondrial function.</p><p><strong>Methods: </strong>Human aortic endothelial cells were exposed to soluble UA and measurements of oxidative stress, nitric oxide, mitochondrial density, ATP production, aconitase-2 and enoyl Co-A hydratase-1 expressions, and aconitase-2 activity in isolated mitochondria were determined. The effect of hyperuricemia induced by uricase inhibition in rats on renal mitochondrial integrity was also assessed.</p><p><strong>Results: </strong>UA-induced endothelial dysfunction was associated with reduced mitochondrial mass and ATP production. UA also decreased aconitase-2 activity and lowered enoyl CoA hydratase-1 expression. Hyperuricemic rats showed increased mitDNA damage in association with higher levels of intrarenal UA and oxidative stress.</p><p><strong>Conclusions: </strong>UA-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP. These studies provide additional evidence for a deleterious effect of UA on vascular function that could be important in the pathogenesis of hypertension and vascular disease.</p>\",\"PeriodicalId\":18993,\"journal\":{\"name\":\"Nephron Experimental Nephrology\",\"volume\":\"121 3-4\",\"pages\":\"e71-8\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2012-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1159/000345509\",\"citationCount\":\"242\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nephron Experimental Nephrology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1159/000345509\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2012/12/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nephron Experimental Nephrology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000345509","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2012/12/7 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 242

摘要

背景/目的:内皮功能障碍与线粒体改变有关。我们假设尿酸(UA)可以在体内和体外诱导内皮功能障碍,也可能改变线粒体功能。方法:将人主动脉内皮细胞暴露于可溶性UA中,测定其氧化应激、一氧化氮、线粒体密度、ATP生成、乌头酶-2和烯丙基辅酶- a水合酶-1表达及乌头酶-2活性。我们还评估了尿酸酶抑制引起的高尿酸血症对大鼠肾线粒体完整性的影响。结果:ua诱导的内皮功能障碍与线粒体质量和ATP生成减少有关。UA还降低了乌头酸酶-2活性,降低了烯丙基辅酶a水合酶-1的表达。高尿酸血症大鼠显示mitDNA损伤增加与较高水平的肾内尿酸和氧化应激有关。结论:ua诱导的内皮功能障碍与线粒体改变和细胞内ATP减少有关。这些研究为UA对血管功能的有害影响提供了额外的证据,这可能在高血压和血管疾病的发病机制中很重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations.

Background/aims: Endothelial dysfunction is associated with mitochondrial alterations. We hypothesized that uric acid (UA), which can induce endothelial dysfunction in vitro and in vivo, might also alter mitochondrial function.

Methods: Human aortic endothelial cells were exposed to soluble UA and measurements of oxidative stress, nitric oxide, mitochondrial density, ATP production, aconitase-2 and enoyl Co-A hydratase-1 expressions, and aconitase-2 activity in isolated mitochondria were determined. The effect of hyperuricemia induced by uricase inhibition in rats on renal mitochondrial integrity was also assessed.

Results: UA-induced endothelial dysfunction was associated with reduced mitochondrial mass and ATP production. UA also decreased aconitase-2 activity and lowered enoyl CoA hydratase-1 expression. Hyperuricemic rats showed increased mitDNA damage in association with higher levels of intrarenal UA and oxidative stress.

Conclusions: UA-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP. These studies provide additional evidence for a deleterious effect of UA on vascular function that could be important in the pathogenesis of hypertension and vascular disease.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Nephron Experimental Nephrology
Nephron Experimental Nephrology 医学-泌尿学与肾脏学
自引率
0.00%
发文量
0
审稿时长
>12 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信