15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90
15-Hydroxyeicosatetraenoic acid (15-HETE), generated by hypoxia, is a product of arachidonic acid and mainly catalyzed by 15-lipoxygenase (15-LO) in pulmonary artery. As HSP90 is known to be involved in apoptosis in other tissues and cells, we aim to test whether anti-apoptotic effect of 15-HETE is...
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| Veröffentlicht in: | Life sciences (1973) 2010-08, Vol.87 (7), p.223-231 |
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| creator | Zhang, Lei Ma, Jun Li, Yaqian Guo, Lei Ran, Yajuan Liu, Shulin Jiang, Chun Zhu, Daling |
| description | 15-Hydroxyeicosatetraenoic acid (15-HETE), generated by hypoxia, is a product of arachidonic acid and mainly catalyzed by 15-lipoxygenase (15-LO) in pulmonary artery. As HSP90 is known to be involved in apoptosis in other tissues and cells, we aim to test whether anti-apoptotic effect of 15-HETE is regulated by the molecular chaperone in pulmonary artery smooth muscle cells.
To test this hypothesis, we performed cell viability analysis, mitochondrial potential assay, caspase-3 activity measurement, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling with and without HSP90 inhibitor.
Our results showed that both exogenous and endogenous 15-HETE up-regulated HSP90 expression and prevented PASMC from serum deprivation-induced apoptosis. Serum deprivation lead to mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, and activation of caspase-3 and caspase-9 in PASMCs. 15-HETE reversed all these effects in a HSP90-dependent manner.
This study establishes the factor involved in 15-HETE-protecting PASMC from apoptosis and the regulation of HSP90 by 15-HETE may be an important mechanism underlying the treatment of pulmonary artery hypertension and provide a novel therapeutic target in future. |
| doi_str_mv | 10.1016/j.lfs.2010.06.019 |
| format | Article |
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To test this hypothesis, we performed cell viability analysis, mitochondrial potential assay, caspase-3 activity measurement, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling with and without HSP90 inhibitor.
Our results showed that both exogenous and endogenous 15-HETE up-regulated HSP90 expression and prevented PASMC from serum deprivation-induced apoptosis. Serum deprivation lead to mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, and activation of caspase-3 and caspase-9 in PASMCs. 15-HETE reversed all these effects in a HSP90-dependent manner.
This study establishes the factor involved in 15-HETE-protecting PASMC from apoptosis and the regulation of HSP90 by 15-HETE may be an important mechanism underlying the treatment of pulmonary artery hypertension and provide a novel therapeutic target in future.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2010.06.019</identifier><identifier>PMID: 20619278</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>15-Hydroxyeicosatetraenoic acid ; Animals ; Apoptosis ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Caspases - genetics ; Caspases - metabolism ; Cell Hypoxia ; Cells, Cultured ; DNA Fragmentation ; Gene Expression Regulation ; Heat shock protein 90 ; HSP90 Heat-Shock Proteins - genetics ; HSP90 Heat-Shock Proteins - metabolism ; Hydroxyeicosatetraenoic Acids - metabolism ; Hypoxia ; Male ; Mitochondria - metabolism ; Myocytes, Smooth Muscle - metabolism ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Pulmonary Artery - cytology ; Rats ; Rats, Wistar</subject><ispartof>Life sciences (1973), 2010-08, Vol.87 (7), p.223-231</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright (c) 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-e516e5f31c0da1512841374a49291b3f044eaeb5f082a0647fe48043cc48fcf83</citedby><cites>FETCH-LOGICAL-c352t-e516e5f31c0da1512841374a49291b3f044eaeb5f082a0647fe48043cc48fcf83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0024320510002717$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20619278$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Ma, Jun</creatorcontrib><creatorcontrib>Li, Yaqian</creatorcontrib><creatorcontrib>Guo, Lei</creatorcontrib><creatorcontrib>Ran, Yajuan</creatorcontrib><creatorcontrib>Liu, Shulin</creatorcontrib><creatorcontrib>Jiang, Chun</creatorcontrib><creatorcontrib>Zhu, Daling</creatorcontrib><title>15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>15-Hydroxyeicosatetraenoic acid (15-HETE), generated by hypoxia, is a product of arachidonic acid and mainly catalyzed by 15-lipoxygenase (15-LO) in pulmonary artery. As HSP90 is known to be involved in apoptosis in other tissues and cells, we aim to test whether anti-apoptotic effect of 15-HETE is regulated by the molecular chaperone in pulmonary artery smooth muscle cells.
To test this hypothesis, we performed cell viability analysis, mitochondrial potential assay, caspase-3 activity measurement, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling with and without HSP90 inhibitor.
Our results showed that both exogenous and endogenous 15-HETE up-regulated HSP90 expression and prevented PASMC from serum deprivation-induced apoptosis. Serum deprivation lead to mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, and activation of caspase-3 and caspase-9 in PASMCs. 15-HETE reversed all these effects in a HSP90-dependent manner.
This study establishes the factor involved in 15-HETE-protecting PASMC from apoptosis and the regulation of HSP90 by 15-HETE may be an important mechanism underlying the treatment of pulmonary artery hypertension and provide a novel therapeutic target in future.</description><subject>15-Hydroxyeicosatetraenoic acid</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Caspases - genetics</subject><subject>Caspases - metabolism</subject><subject>Cell Hypoxia</subject><subject>Cells, Cultured</subject><subject>DNA Fragmentation</subject><subject>Gene Expression Regulation</subject><subject>Heat shock protein 90</subject><subject>HSP90 Heat-Shock Proteins - genetics</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Hydroxyeicosatetraenoic Acids - metabolism</subject><subject>Hypoxia</subject><subject>Male</subject><subject>Mitochondria - metabolism</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Pulmonary Artery - cytology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE2LFDEQhoMo7rj6A7xIbuqhx8pXf-BJltERFhRczyGTrtYM3Z02lV6cf2-GWT16Kgqe96XqYeylgK0AUb87bseBthLKDvUWRPeIbUTbdBXUSjxmGwCpKyXBXLFnREcAMKZRT9mVhFp0smk3jISp9qc-xd8nDD6Sy5iTwzkGz50PPX9zBnZ3u7d8STGjz8SXdZzi7NKJu5SxDJpizD_5tJIfkXscR-LuhwszZe6WuORIgfh9cHz_7WsHz9mTwY2ELx7mNfv-cXd3s69uv3z6fPPhtvLKyFyhETWaQQkPvRNGyFYL1WinO9mJgxpAa3R4MAO00kGtmwF1C1p5r9vBD626Zq8vveXyXytStlOg83VuxriSbXTbaTBaF1JcSJ8iUcLBLilM5UMrwJ5V26Mtqu1ZtYXaFtUl8-qhfT1M2P9L_HVbgPcXAMuP9wGTJR9w9tiHVDzaPob_1P8BQHCOyg</recordid><startdate>20100814</startdate><enddate>20100814</enddate><creator>Zhang, Lei</creator><creator>Ma, Jun</creator><creator>Li, Yaqian</creator><creator>Guo, Lei</creator><creator>Ran, Yajuan</creator><creator>Liu, Shulin</creator><creator>Jiang, Chun</creator><creator>Zhu, Daling</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>7X8</scope></search><sort><creationdate>20100814</creationdate><title>15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90</title><author>Zhang, Lei ; Ma, Jun ; Li, Yaqian ; Guo, Lei ; Ran, Yajuan ; Liu, Shulin ; Jiang, Chun ; Zhu, Daling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-e516e5f31c0da1512841374a49291b3f044eaeb5f082a0647fe48043cc48fcf83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>15-Hydroxyeicosatetraenoic acid</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Caspases - genetics</topic><topic>Caspases - metabolism</topic><topic>Cell Hypoxia</topic><topic>Cells, Cultured</topic><topic>DNA Fragmentation</topic><topic>Gene Expression Regulation</topic><topic>Heat shock protein 90</topic><topic>HSP90 Heat-Shock Proteins - genetics</topic><topic>HSP90 Heat-Shock Proteins - metabolism</topic><topic>Hydroxyeicosatetraenoic Acids - metabolism</topic><topic>Hypoxia</topic><topic>Male</topic><topic>Mitochondria - metabolism</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Pulmonary Artery - cytology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Lei</creatorcontrib><creatorcontrib>Ma, Jun</creatorcontrib><creatorcontrib>Li, Yaqian</creatorcontrib><creatorcontrib>Guo, Lei</creatorcontrib><creatorcontrib>Ran, Yajuan</creatorcontrib><creatorcontrib>Liu, Shulin</creatorcontrib><creatorcontrib>Jiang, Chun</creatorcontrib><creatorcontrib>Zhu, Daling</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Lei</au><au>Ma, Jun</au><au>Li, Yaqian</au><au>Guo, Lei</au><au>Ran, Yajuan</au><au>Liu, Shulin</au><au>Jiang, Chun</au><au>Zhu, Daling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2010-08-14</date><risdate>2010</risdate><volume>87</volume><issue>7</issue><spage>223</spage><epage>231</epage><pages>223-231</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>15-Hydroxyeicosatetraenoic acid (15-HETE), generated by hypoxia, is a product of arachidonic acid and mainly catalyzed by 15-lipoxygenase (15-LO) in pulmonary artery. As HSP90 is known to be involved in apoptosis in other tissues and cells, we aim to test whether anti-apoptotic effect of 15-HETE is regulated by the molecular chaperone in pulmonary artery smooth muscle cells.
To test this hypothesis, we performed cell viability analysis, mitochondrial potential assay, caspase-3 activity measurement, Western blot, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling with and without HSP90 inhibitor.
Our results showed that both exogenous and endogenous 15-HETE up-regulated HSP90 expression and prevented PASMC from serum deprivation-induced apoptosis. Serum deprivation lead to mitochondrial membrane depolarization, decreased expression of Bcl-2 and enhanced expression of Bax, and activation of caspase-3 and caspase-9 in PASMCs. 15-HETE reversed all these effects in a HSP90-dependent manner.
This study establishes the factor involved in 15-HETE-protecting PASMC from apoptosis and the regulation of HSP90 by 15-HETE may be an important mechanism underlying the treatment of pulmonary artery hypertension and provide a novel therapeutic target in future.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>20619278</pmid><doi>10.1016/j.lfs.2010.06.019</doi><tpages>9</tpages></addata></record> |
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| subjects | 15-Hydroxyeicosatetraenoic acid Animals Apoptosis bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Caspases - genetics Caspases - metabolism Cell Hypoxia Cells, Cultured DNA Fragmentation Gene Expression Regulation Heat shock protein 90 HSP90 Heat-Shock Proteins - genetics HSP90 Heat-Shock Proteins - metabolism Hydroxyeicosatetraenoic Acids - metabolism Hypoxia Male Mitochondria - metabolism Myocytes, Smooth Muscle - metabolism Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Pulmonary Artery - cytology Rats Rats, Wistar |
| title | 15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90 |
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