Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis
The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (...
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| Veröffentlicht in: | Molecular biology reports 2019-08, Vol.46 (4), p.3809-3816 |
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| creator | Zhu, Yanji Li, Qian Xun, Wenlong Chen, Yuan Zhang, Caihui Sun, Shuzhen |
| description | The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated. |
| doi_str_mv | 10.1007/s11033-019-04823-6 |
| format | Article |
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Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-019-04823-6</identifier><identifier>PMID: 31004300</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animal Anatomy ; Animal Biochemistry ; Apoptosis ; Apoptosis - drug effects ; Bax protein ; bcl-2-Associated X Protein - metabolism ; Biomedical and Life Sciences ; Caspase ; Caspase 3 - metabolism ; Caspase-3 ; Cell Line ; Histology ; Humans ; Immunofluorescence ; Life Sciences ; Lipoproteins, LDL - pharmacology ; Low density lipoprotein ; Morphology ; Original Article ; Podocytes - drug effects ; Podocytes - metabolism ; Pyridines - pharmacology ; Reactive Oxygen Species - metabolism ; Receptors, Purinergic P2X7 - drug effects ; Receptors, Purinergic P2X7 - metabolism ; Tetrazoles - pharmacology</subject><ispartof>Molecular biology reports, 2019-08, Vol.46 (4), p.3809-3816</ispartof><rights>Springer Nature B.V. 2019</rights><rights>Molecular Biology Reports is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-3a91cc7c75a03cedade9a4ea619d786af62e91c5bdd8dabfbb65218791dee3663</citedby><cites>FETCH-LOGICAL-c375t-3a91cc7c75a03cedade9a4ea619d786af62e91c5bdd8dabfbb65218791dee3663</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-019-04823-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-019-04823-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31004300$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Yanji</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Xun, Wenlong</creatorcontrib><creatorcontrib>Chen, Yuan</creatorcontrib><creatorcontrib>Zhang, Caihui</creatorcontrib><creatorcontrib>Sun, Shuzhen</creatorcontrib><title>Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><addtitle>Mol Biol Rep</addtitle><description>The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated.</description><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bax protein</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Caspase</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase-3</subject><subject>Cell Line</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Life Sciences</subject><subject>Lipoproteins, LDL - pharmacology</subject><subject>Low density lipoprotein</subject><subject>Morphology</subject><subject>Original Article</subject><subject>Podocytes - drug effects</subject><subject>Podocytes - metabolism</subject><subject>Pyridines - pharmacology</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptors, Purinergic P2X7 - drug effects</subject><subject>Receptors, Purinergic P2X7 - metabolism</subject><subject>Tetrazoles - pharmacology</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kMtOwzAQRS0EouXxAyxQJDZsDH7EcbKE8hSVYAESO8uxJ1VKWgc7lShfj9sUkFiwsjQ-987oIHREyRklRJ4HSgnnmNACkzRnHGdbaEiF5DgtZL6NhoQTitNc0AHaC2FKCEmpFLtowGM-5YQM0cNl48xbPZ8kT-xVJh4MtJ3ziZ5BUzuvOwiJ-6ht_Qk2GV-N8QxsHac2aZ11ZtlBolsXI6EOB2in0k2Aw827j15urp9Hd3j8eHs_uhhjw6XoMNcFNUYaKTThBqy2UOgUdEYLK_NMVxmDSIjS2tzqsirLTDCay4JaAJ5lfB-d9r2td-8LCJ2a1cFA0-g5uEVQjFFapIUQJKInf9CpW_h5vG5NpXmeMRYp1lPGuxA8VKr19Uz7paJErVSrXrWKqtVatVpdcbypXpRRyk_k220EeA-E-DWfgP_d_U_tF7ASiUY</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Zhu, Yanji</creator><creator>Li, Qian</creator><creator>Xun, Wenlong</creator><creator>Chen, Yuan</creator><creator>Zhang, Caihui</creator><creator>Sun, Shuzhen</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20190801</creationdate><title>Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis</title><author>Zhu, Yanji ; Li, Qian ; Xun, Wenlong ; Chen, Yuan ; Zhang, Caihui ; Sun, Shuzhen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-3a91cc7c75a03cedade9a4ea619d786af62e91c5bdd8dabfbb65218791dee3663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animal Anatomy</topic><topic>Animal Biochemistry</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bax protein</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Caspase</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase-3</topic><topic>Cell Line</topic><topic>Histology</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Life Sciences</topic><topic>Lipoproteins, LDL - pharmacology</topic><topic>Low density lipoprotein</topic><topic>Morphology</topic><topic>Original Article</topic><topic>Podocytes - drug effects</topic><topic>Podocytes - metabolism</topic><topic>Pyridines - pharmacology</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Receptors, Purinergic P2X7 - drug effects</topic><topic>Receptors, Purinergic P2X7 - metabolism</topic><topic>Tetrazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Yanji</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Xun, Wenlong</creatorcontrib><creatorcontrib>Chen, Yuan</creatorcontrib><creatorcontrib>Zhang, Caihui</creatorcontrib><creatorcontrib>Sun, Shuzhen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular biology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Yanji</au><au>Li, Qian</au><au>Xun, Wenlong</au><au>Chen, Yuan</au><au>Zhang, Caihui</au><au>Sun, Shuzhen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><addtitle>Mol Biol Rep</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>46</volume><issue>4</issue><spage>3809</spage><epage>3816</epage><pages>3809-3816</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract>The purpose of our research is to elucidate whether oxLDL activates P2X7R in cultured human podocytes and if the activation of P2X7R leads to podocyte apoptosis. Additionally, we explore the underlying mechanism involved in podocyte apoptosis. Immortalized human podocytes were incubated with oxLDL (80 µg/ml), P2X7R antagonist A438079 (10 µM), or the compound of A438079 and oxLDL for 48 h, respectively. Cellular apoptosis and ROS were evaluated using flow cytometer. P2X7R, Bax, and Caspase-3 protein expression were detected by western blot and immunofluorescence analysis.The expression of P2X7R, ROS, Bax, and Caspase-3 in human podocytes incubated with oxLDL was significantly up-regulated and was found to have higher intracellular lipid accumulation and podocyte apoptosis compared with the NC group. However, co-administration with A438079, ROS, Bax, and Caspase-3 expression both significantly down-regulate as well as lower lipid accumulation and cellular apoptosis in the oxLDL-induced podocyte group. We revealed that P2X7R is involved in the regulation of oxLDL-treated podocytes. Additionally, we found that the anti-apoptotic effect of A438079 is correlated with ROS, Bax, and Caspase-3 expression down-regulated.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>31004300</pmid><doi>10.1007/s11033-019-04823-6</doi><tpages>8</tpages></addata></record> |
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| subjects | Animal Anatomy Animal Biochemistry Apoptosis Apoptosis - drug effects Bax protein bcl-2-Associated X Protein - metabolism Biomedical and Life Sciences Caspase Caspase 3 - metabolism Caspase-3 Cell Line Histology Humans Immunofluorescence Life Sciences Lipoproteins, LDL - pharmacology Low density lipoprotein Morphology Original Article Podocytes - drug effects Podocytes - metabolism Pyridines - pharmacology Reactive Oxygen Species - metabolism Receptors, Purinergic P2X7 - drug effects Receptors, Purinergic P2X7 - metabolism Tetrazoles - pharmacology |
| title | Blocking P2X7 receptor ameliorates oxidized LDL-mediated podocyte apoptosis |
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