The Efficacy of Puromycin and Adriamycin for Induction of Glomerular Failure in Larval Zebrafish Validated by an Assay of Glomerular Permeability Dynamics
Defects in the glomerular filtration barrier (GFB) play a major role in the onset of human renal diseases. Highly ramified glomerular cells named podocytes are a critical component of the GFB. Injury to podocytes results in abnormal excretion of plasma proteins, which can lead to chronic kidney dise...
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Veröffentlicht in: | Zebrafish 2018-06, Vol.15 (3), p.234-242 |
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description | Defects in the glomerular filtration barrier (GFB) play a major role in the onset of human renal diseases. Highly ramified glomerular cells named podocytes are a critical component of the GFB. Injury to podocytes results in abnormal excretion of plasma proteins, which can lead to chronic kidney disease. The conserved paired nephron of larval zebrafish is an excellent model for assessing glomerular function and injury. The efficacy of two known podocyte toxins was tested to refine models of acute podocyte injury in larval zebrafish. The validated compound was then used to test a novel assay of the dynamics of abnormal protein excretion. Injected adriamycin was found to be unsuitable for induction of glomerular injury due to off-target cardiovascular toxicity. In contrast, puromycin treatment resulted in a loss of discriminative filtration, measured by excretion of 70 kDa dextran, and podocyte effacement confirmed by electron microscopy. The dynamics of dextran excretion during puromycin injury modeled the onset of glomerular damage within 24 hours postinjection. These data validate puromycin for induction of acute podocyte injury in zebrafish larvae and describe a semihigh-throughput assay for quantifying the dynamics of abnormal protein excretion. |
doi_str_mv | 10.1089/zeb.2017.1527 |
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Highly ramified glomerular cells named podocytes are a critical component of the GFB. Injury to podocytes results in abnormal excretion of plasma proteins, which can lead to chronic kidney disease. The conserved paired nephron of larval zebrafish is an excellent model for assessing glomerular function and injury. The efficacy of two known podocyte toxins was tested to refine models of acute podocyte injury in larval zebrafish. The validated compound was then used to test a novel assay of the dynamics of abnormal protein excretion. Injected adriamycin was found to be unsuitable for induction of glomerular injury due to off-target cardiovascular toxicity. In contrast, puromycin treatment resulted in a loss of discriminative filtration, measured by excretion of 70 kDa dextran, and podocyte effacement confirmed by electron microscopy. The dynamics of dextran excretion during puromycin injury modeled the onset of glomerular damage within 24 hours postinjection. 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These data validate puromycin for induction of acute podocyte injury in zebrafish larvae and describe a semihigh-throughput assay for quantifying the dynamics of abnormal protein excretion.</description><subject>Assaying</subject><subject>Critical components</subject><subject>Danio rerio</subject><subject>Defects</subject><subject>Dextran</subject><subject>Dynamics</subject><subject>Electron microscopy</subject><subject>Excretion</subject><subject>Filtration</subject><subject>Freshwater fishes</subject><subject>Injuries</subject><subject>Larvae</subject><subject>Original</subject><subject>Original Articles</subject><subject>Permeability</subject><subject>Plasma proteins</subject><subject>Proteins</subject><subject>Puromycin</subject><subject>Toxicity</subject><subject>Toxins</subject><subject>Zebrafish</subject><issn>1545-8547</issn><issn>1557-8542</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>1-M</sourceid><recordid>eNqFkcFu1DAQhiMEoqVw5Ioscc7WduIkviCtSlsqrUQPhQMXa2yPWVeJXeykUngUnpZE21bAhZPH48__jPQVxVtGN4x28vQn6g2nrN0wwdtnxTEToi07UfPna12LtW6Pilc531JaVbKqXxZHXNYdbWV1XPy62SM5d84bMDOJjlxPKQ6z8YFAsGRrk4fD1cVEroKdzOhjWMnLPg6Yph4SuQDfTwnJgu0g3UNPvqFO4Hzek6_QewsjWqLnJZNsc4b5n__XmAYE7Xs_zuTjHGDwJr8uXjjoM755OE-KLxfnN2efyt3ny6uz7a40tZBjCVrXjeTSWcs4F21rZSewodp21FWSSdtUzqBuuBFUd-AawR3vmoZViDVCdVJ8OOTeTXpAazCMCXp1l_wAaVYRvPr7Jfi9-h7vlVgGSUaXgPcPASn-mDCP6jZOKSw7K04FbRhnTb1Q5YEyKeac0D1NYFStKtWiUq0q1apy4d_9udYT_ehuAaoDsLYhhN6jxjT-J_Y3fZWu4Q</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Rider, Sebastien Andrew</creator><creator>Bruton, Finnius Austin</creator><creator>Collins, Richard George</creator><creator>Conway, Bryan Ronald</creator><creator>Mullins, John James</creator><general>Mary Ann Liebert, Inc</general><scope>1-M</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7T5</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>F1W</scope><scope>FR3</scope><scope>H94</scope><scope>H95</scope><scope>H98</scope><scope>H99</scope><scope>L.F</scope><scope>L.G</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20180601</creationdate><title>The Efficacy of Puromycin and Adriamycin for Induction of Glomerular Failure in Larval Zebrafish Validated by an Assay of Glomerular Permeability Dynamics</title><author>Rider, Sebastien Andrew ; Bruton, Finnius Austin ; Collins, Richard George ; Conway, Bryan Ronald ; Mullins, John James</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-abb46929fdd122577d985e60bd80f3919d63fceb62c50b8af652f286613ee4ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Assaying</topic><topic>Critical components</topic><topic>Danio rerio</topic><topic>Defects</topic><topic>Dextran</topic><topic>Dynamics</topic><topic>Electron microscopy</topic><topic>Excretion</topic><topic>Filtration</topic><topic>Freshwater fishes</topic><topic>Injuries</topic><topic>Larvae</topic><topic>Original</topic><topic>Original Articles</topic><topic>Permeability</topic><topic>Plasma proteins</topic><topic>Proteins</topic><topic>Puromycin</topic><topic>Toxicity</topic><topic>Toxins</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rider, Sebastien Andrew</creatorcontrib><creatorcontrib>Bruton, Finnius Austin</creatorcontrib><creatorcontrib>Collins, Richard George</creatorcontrib><creatorcontrib>Conway, Bryan Ronald</creatorcontrib><creatorcontrib>Mullins, John James</creatorcontrib><collection>Mary Ann Liebert Online - Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Aquaculture Abstracts</collection><collection>ASFA: Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Marine Biotechnology Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Zebrafish</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rider, Sebastien Andrew</au><au>Bruton, Finnius Austin</au><au>Collins, Richard George</au><au>Conway, Bryan Ronald</au><au>Mullins, John James</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Efficacy of Puromycin and Adriamycin for Induction of Glomerular Failure in Larval Zebrafish Validated by an Assay of Glomerular Permeability Dynamics</atitle><jtitle>Zebrafish</jtitle><addtitle>Zebrafish</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>15</volume><issue>3</issue><spage>234</spage><epage>242</epage><pages>234-242</pages><issn>1545-8547</issn><eissn>1557-8542</eissn><abstract>Defects in the glomerular filtration barrier (GFB) play a major role in the onset of human renal diseases. Highly ramified glomerular cells named podocytes are a critical component of the GFB. Injury to podocytes results in abnormal excretion of plasma proteins, which can lead to chronic kidney disease. The conserved paired nephron of larval zebrafish is an excellent model for assessing glomerular function and injury. The efficacy of two known podocyte toxins was tested to refine models of acute podocyte injury in larval zebrafish. The validated compound was then used to test a novel assay of the dynamics of abnormal protein excretion. Injected adriamycin was found to be unsuitable for induction of glomerular injury due to off-target cardiovascular toxicity. In contrast, puromycin treatment resulted in a loss of discriminative filtration, measured by excretion of 70 kDa dextran, and podocyte effacement confirmed by electron microscopy. The dynamics of dextran excretion during puromycin injury modeled the onset of glomerular damage within 24 hours postinjection. 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subjects | Assaying Critical components Danio rerio Defects Dextran Dynamics Electron microscopy Excretion Filtration Freshwater fishes Injuries Larvae Original Original Articles Permeability Plasma proteins Proteins Puromycin Toxicity Toxins Zebrafish |
title | The Efficacy of Puromycin and Adriamycin for Induction of Glomerular Failure in Larval Zebrafish Validated by an Assay of Glomerular Permeability Dynamics |
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