Protection of the transplant kidney during cold perfusion with doxycycline: proteomic analysis in a rat model.

IF 2.1 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Proteome Science Pub Date : 2020-04-20 eCollection Date: 2020-01-01 DOI:10.1186/s12953-020-00159-3

Michael A J Moser, Katherine Sawicka, Jolanta Sawicka, Aleksandra Franczak, Alejandro Cohen, Iwona Bil-Lula, Grzegorz Sawicki

{"title":"Protection of the transplant kidney during cold perfusion with doxycycline: proteomic analysis in a rat model.","authors":"Michael A J Moser, Katherine Sawicka, Jolanta Sawicka, Aleksandra Franczak, Alejandro Cohen, Iwona Bil-Lula, Grzegorz Sawicki","doi":"10.1186/s12953-020-00159-3","DOIUrl":null,"url":null,"abstract":"Background: It has been previously shown that doxycycline (Doxy) protects the kidney from preservation injury by inhibition of matrix metalloproteinase. However, the precise molecular mechanism involved in this protection from injury is not known. We used a pharmaco-proteomics approach to identify potential molecular targets associated with kidney preservation injury.Methods: Rat kidneys were cold perfused with or without doxycycline (Doxy) for 22 h. Kidneys perfusates were analyzed for the presence of injury markers such as lactate dehydrogenase (LDH), and neutrophil-gelatinase associated lipocalin (NGAL). Proteins extracted from kidney tissue were analyzed by 2-dimensional gel electrophoresis. Proteins of interest were identified by mass spectrometry.Results: Triosephosphate isomerase, PGM, dihydropteridine reductase-2, pyridine nucleotide-disulfide oxidoreductase, phosphotriesterase-related protein, and aminoacylase-1A were not affected by cold perfusion. Perfusion with Doxy increased their levels. N(G),N(G)-dimethylarginine dimethylaminohydrolase and phosphoglycerate kinase 1 were decreased after cold perfusion. Perfusion with Doxy led to an increase in their levels.Conclusions: This study revealed specific metabolic enzymes involved in preservation injury and in the mechanism whereby Doxy protects the kidney against injury during cold perfusion.","PeriodicalId":20857,"journal":{"name":"Proteome Science","volume":"18 ","pages":"3"},"PeriodicalIF":2.1000,"publicationDate":"2020-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171734/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteome Science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12953-020-00159-3","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: It has been previously shown that doxycycline (Doxy) protects the kidney from preservation injury by inhibition of matrix metalloproteinase. However, the precise molecular mechanism involved in this protection from injury is not known. We used a pharmaco-proteomics approach to identify potential molecular targets associated with kidney preservation injury.

Methods: Rat kidneys were cold perfused with or without doxycycline (Doxy) for 22 h. Kidneys perfusates were analyzed for the presence of injury markers such as lactate dehydrogenase (LDH), and neutrophil-gelatinase associated lipocalin (NGAL). Proteins extracted from kidney tissue were analyzed by 2-dimensional gel electrophoresis. Proteins of interest were identified by mass spectrometry.

Results: Triosephosphate isomerase, PGM, dihydropteridine reductase-2, pyridine nucleotide-disulfide oxidoreductase, phosphotriesterase-related protein, and aminoacylase-1A were not affected by cold perfusion. Perfusion with Doxy increased their levels. N(G),N(G)-dimethylarginine dimethylaminohydrolase and phosphoglycerate kinase 1 were decreased after cold perfusion. Perfusion with Doxy led to an increase in their levels.

Conclusions: This study revealed specific metabolic enzymes involved in preservation injury and in the mechanism whereby Doxy protects the kidney against injury during cold perfusion.

Abstract Image

查看原文本刊更多论文

多西环素冷灌注期间对移植肾的保护：大鼠模型的蛋白质组分析。

背景：以前的研究表明，强力霉素（Doxy）通过抑制基质金属蛋白酶保护肾脏免受保存损伤。然而，这种保护肾脏免受损伤的确切分子机制尚不清楚。我们采用药物蛋白组学方法来确定与肾脏保存损伤相关的潜在分子靶点：分析肾脏灌流液中是否存在损伤标志物，如乳酸脱氢酶（LDH）和中性粒细胞-明胶酶相关脂质体蛋白（NGAL）。通过二维凝胶电泳分析从肾组织中提取的蛋白质。相关蛋白质通过质谱进行鉴定：结果：三磷酸异构酶、PGM、二氢吡啶还原酶-2、吡啶核苷酸-二硫氧化还原酶、磷酸三酯酶相关蛋白和氨基酰化酶-1A不受冷灌流的影响。灌注强力霉素可提高它们的水平。冷灌注后，N(G),N(G)-二甲基精氨酸二甲氨基水合酶和磷酸甘油酸激酶 1 的水平下降。结论：该研究揭示了特定的代谢酶：这项研究揭示了参与保存损伤的特定代谢酶，以及强力素在冷灌注过程中保护肾脏免受损伤的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Proteome Science 生物-生化研究方法

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

4.5 months

期刊介绍： Proteome Science is an open access journal publishing research in the area of systems studies. Proteome Science considers manuscripts based on all aspects of functional and structural proteomics, genomics, metabolomics, systems analysis and metabiome analysis. It encourages the submissions of studies that use large-scale or systems analysis of biomolecules in a cellular, organismal and/or environmental context. Studies that describe novel biological or clinical insights as well as methods-focused studies that describe novel methods for the large-scale study of any and all biomolecules in cells and tissues, such as mass spectrometry, protein and nucleic acid microarrays, genomics, next-generation sequencing and computational algorithms and methods are all within the scope of Proteome Science, as are electron topography, structural methods, proteogenomics, chemical proteomics, stem cell proteomics, organelle proteomics, plant and microbial proteomics. In spite of its name, Proteome Science considers all aspects of large-scale and systems studies because ultimately any mechanism that results in genomic and metabolomic changes will affect or be affected by the proteome. To reflect this intrinsic relationship of biological systems, Proteome Science will consider all such articles.