Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes

Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, change...

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Veröffentlicht in:Toxicology and applied pharmacology 2017-03, Vol.318, p.41-48
Hauptverfasser: Lu, Yin, Wang, Jianshe, Guo, Xuejiang, Yan, Shengmin, Dai, Jiayin
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Wang, Jianshe
Guo, Xuejiang
Yan, Shengmin
Dai, Jiayin
description Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P
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Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (&gt;1.5-fold and P&lt;0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. •Endocytosis and blood-testis barrier proteins were changed after PFOA exposure.•Seventeen miRNAs were differentially expressed in testes after PFOA exposure.•MiRNAs might play a role in gene regulation in testes after PFOA exposure.CLTA is a potential target of miR-133b-3p.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2017.01.014</identifier><identifier>PMID: 28126411</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Animals ; APOLIPOPROTEINS ; BLOOD ; Caprylates - toxicity ; Clathrin Light Chains - biosynthesis ; CLTA ; CONSUMER PRODUCTS ; Endocytosis ; Endocytosis - drug effects ; Endocytosis - physiology ; Fluorocarbons - toxicity ; GENE REGULATION ; GROWTH FACTORS ; HEALTH HAZARDS ; IN VITRO ; LUCIFERASE ; Male ; MICE ; Mice, Inbred BALB C ; MicroRNAs - biosynthesis ; miRNA ; Perfluorooctanoic acid ; Protein Interaction Maps - drug effects ; Protein Interaction Maps - physiology ; Random Allocation ; RECEPTORS ; SERINE ; TESTES ; Testis - drug effects ; Testis - metabolism</subject><ispartof>Toxicology and applied pharmacology, 2017-03, Vol.318, p.41-48</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. 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Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (&gt;1.5-fold and P&lt;0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. •Endocytosis and blood-testis barrier proteins were changed after PFOA exposure.•Seventeen miRNAs were differentially expressed in testes after PFOA exposure.•MiRNAs might play a role in gene regulation in testes after PFOA exposure.CLTA is a potential target of miR-133b-3p.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Animals</subject><subject>APOLIPOPROTEINS</subject><subject>BLOOD</subject><subject>Caprylates - toxicity</subject><subject>Clathrin Light Chains - biosynthesis</subject><subject>CLTA</subject><subject>CONSUMER PRODUCTS</subject><subject>Endocytosis</subject><subject>Endocytosis - drug effects</subject><subject>Endocytosis - physiology</subject><subject>Fluorocarbons - toxicity</subject><subject>GENE REGULATION</subject><subject>GROWTH FACTORS</subject><subject>HEALTH HAZARDS</subject><subject>IN VITRO</subject><subject>LUCIFERASE</subject><subject>Male</subject><subject>MICE</subject><subject>Mice, Inbred BALB C</subject><subject>MicroRNAs - biosynthesis</subject><subject>miRNA</subject><subject>Perfluorooctanoic acid</subject><subject>Protein Interaction Maps - drug effects</subject><subject>Protein Interaction Maps - physiology</subject><subject>Random Allocation</subject><subject>RECEPTORS</subject><subject>SERINE</subject><subject>TESTES</subject><subject>Testis - drug effects</subject><subject>Testis - metabolism</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UE1rGzEUFKWlcdL-gR6KoOd1nz5Wu4JeTEiaQmhDaKE3IesjlllLiyQb8u-jxW2PhYH3DjPz3gxCHwisCRDxeb-uWs9rCmRYA2ngr9CKgBQdMMZeoxUAJx3A-PsCXZayBwDJOXmLLuhIqOCErND84LKfjimnZKqOKRisTbBYe-9MLdhFm8xzTSUUHOIpTacQn7CZdN3lEPEUnnYVm51u-wbraPEhmJwev286wti2Y3NT4UM6FoerKw3v0Buvp-Le_5lX6Nftzc_ru-7-x9dv15v7zrCR1855J3rn2VbQfuBDLw2VvZQ9UD76QYOjdDSjF6NlgjpqtRjoVjLegwdLh5FdoU9n31RqUMWE6szOpBhbLEWpkCAZbSx6ZrWnS8nOqzmHg87PioBaSlZ7tZSslpIVkAbeRB_Povm4PTj7T_K31Ub4cia4FvAUXF7uu2icDXk5b1P4n_8LYi6NMA</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Lu, Yin</creator><creator>Wang, Jianshe</creator><creator>Guo, Xuejiang</creator><creator>Yan, Shengmin</creator><creator>Dai, Jiayin</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>OTOTI</scope></search><sort><creationdate>20170301</creationdate><title>Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes</title><author>Lu, Yin ; Wang, Jianshe ; Guo, Xuejiang ; Yan, Shengmin ; Dai, Jiayin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-efe65ef3b62574759c2959950248f7a0e228c8f68d362e2da672b93450f0d2783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Animals</topic><topic>APOLIPOPROTEINS</topic><topic>BLOOD</topic><topic>Caprylates - toxicity</topic><topic>Clathrin Light Chains - biosynthesis</topic><topic>CLTA</topic><topic>CONSUMER PRODUCTS</topic><topic>Endocytosis</topic><topic>Endocytosis - drug effects</topic><topic>Endocytosis - physiology</topic><topic>Fluorocarbons - toxicity</topic><topic>GENE REGULATION</topic><topic>GROWTH FACTORS</topic><topic>HEALTH HAZARDS</topic><topic>IN VITRO</topic><topic>LUCIFERASE</topic><topic>Male</topic><topic>MICE</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs - biosynthesis</topic><topic>miRNA</topic><topic>Perfluorooctanoic acid</topic><topic>Protein Interaction Maps - drug effects</topic><topic>Protein Interaction Maps - physiology</topic><topic>Random Allocation</topic><topic>RECEPTORS</topic><topic>SERINE</topic><topic>TESTES</topic><topic>Testis - drug effects</topic><topic>Testis - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Yin</creatorcontrib><creatorcontrib>Wang, Jianshe</creatorcontrib><creatorcontrib>Guo, Xuejiang</creatorcontrib><creatorcontrib>Yan, Shengmin</creatorcontrib><creatorcontrib>Dai, Jiayin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Yin</au><au>Wang, Jianshe</au><au>Guo, Xuejiang</au><au>Yan, Shengmin</au><au>Dai, Jiayin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>318</volume><spage>41</spage><epage>48</epage><pages>41-48</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (&gt;1.5-fold and P&lt;0.05 compared with the control). Eight of these miRNAs were further selected for TaqMan qPCR analysis. Proteomic profile analysis indicated that many changed proteins after PFOA treatment, including intersectin 1 (ITSN1), serine protease inhibitor A3K (Serpina3k), and apolipoprotein a1 (APOA1), were involved in endocytosis and blood-testis barrier (BTB) processes. These changes were further verified by immunohistochemical and Western blot analyses. Endocytosis-related genes were selected for qPCR analysis, with many found to be significantly changed after PFOA treatment, including epidermal growth factor receptor pathway substrate 8 (Eps8), Eps15, cortactin, cofilin, espin, vinculin, and zyxin. We further predicted the potential interaction between changed miRNAs and proteins, which indicated that miRNAs might play a role in the post-translational regulation of gene expression after PFOA treatment in mouse testes. Among them, miR-133b-3p/clathrin light chain A (CLTA) was selected and verified in vitro by transfection and luciferase activity assay. Results showed that PFOA exposure affects endocytosis in mouse testes and that CLTA is a potential target of miR-133b-3p. •Endocytosis and blood-testis barrier proteins were changed after PFOA exposure.•Seventeen miRNAs were differentially expressed in testes after PFOA exposure.•MiRNAs might play a role in gene regulation in testes after PFOA exposure.CLTA is a potential target of miR-133b-3p.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28126411</pmid><doi>10.1016/j.taap.2017.01.014</doi><tpages>8</tpages></addata></record>
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subjects 60 APPLIED LIFE SCIENCES
Animals
APOLIPOPROTEINS
BLOOD
Caprylates - toxicity
Clathrin Light Chains - biosynthesis
CLTA
CONSUMER PRODUCTS
Endocytosis
Endocytosis - drug effects
Endocytosis - physiology
Fluorocarbons - toxicity
GENE REGULATION
GROWTH FACTORS
HEALTH HAZARDS
IN VITRO
LUCIFERASE
Male
MICE
Mice, Inbred BALB C
MicroRNAs - biosynthesis
miRNA
Perfluorooctanoic acid
Protein Interaction Maps - drug effects
Protein Interaction Maps - physiology
Random Allocation
RECEPTORS
SERINE
TESTES
Testis - drug effects
Testis - metabolism
title Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes
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