Altered subcellular localization of heat shock protein 90 is associated with impaired expression of the aryl hydrocarbon receptor pathway in dogs
The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein...
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| Veröffentlicht in: | PloS one 2013-03, Vol.8 (3), p.e57973 |
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| creator | van Steenbeek, Frank G Spee, Bart Penning, Louis C Kummeling, Anne van Gils, Ingrid H M Grinwis, Guy C M Van Leenen, Dik Holstege, Frank C P Vos-Loohuis, Manon Rothuizen, Jan Leegwater, Peter A J |
| description | The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhound. We compared the expression of components of the AHR pathway in healthy Irish wolfhounds and dogs with IHPSS. To this end, we analyzed the mRNA expression in the liver of AHR,AIP, ARNT, and other genes involved in this pathway, namely, those for aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), hypoxia inducible factor 1alpha (HIF1A), heat shock protein 90AA1 (HSP90AA1), cytochromes P450 (CYP1A1, CYP1A2, and CYP1B1), vascular endothelial growth factor A (VEGFA), nitric oxide synthesase 3 (NOS3), and endothelin (EDN1). The observed low expression of AHR mRNA in the Irish wolfhounds is in associated with a LINE-1 insertion in intron 2, for which these dogs were homozygous. Down regulation in Irish wolfhounds was observed for AIP, ARNT2, CYP1A2, CYP1B1 and HSP90AA1 expression, whereas the expression of HIF1A was increased. Immunohistochemistry revealed lower levels of AHR, HIF1A, and VEGFA protein in the nucleus and lower levels of ARNT and HSP90AA1 protein in the cytoplasm of the liver cells of Irish wolfhounds. The impaired expression of HSP90AA1 could trigger the observed differences in mRNA and protein levels and therefore explain the link between two very different functions of AHR: regulation of the closure of the ductus venosus and the response to toxins. |
| doi_str_mv | 10.1371/journal.pone.0057973 |
| format | Article |
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An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhound. We compared the expression of components of the AHR pathway in healthy Irish wolfhounds and dogs with IHPSS. To this end, we analyzed the mRNA expression in the liver of AHR,AIP, ARNT, and other genes involved in this pathway, namely, those for aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), hypoxia inducible factor 1alpha (HIF1A), heat shock protein 90AA1 (HSP90AA1), cytochromes P450 (CYP1A1, CYP1A2, and CYP1B1), vascular endothelial growth factor A (VEGFA), nitric oxide synthesase 3 (NOS3), and endothelin (EDN1). The observed low expression of AHR mRNA in the Irish wolfhounds is in associated with a LINE-1 insertion in intron 2, for which these dogs were homozygous. Down regulation in Irish wolfhounds was observed for AIP, ARNT2, CYP1A2, CYP1B1 and HSP90AA1 expression, whereas the expression of HIF1A was increased. Immunohistochemistry revealed lower levels of AHR, HIF1A, and VEGFA protein in the nucleus and lower levels of ARNT and HSP90AA1 protein in the cytoplasm of the liver cells of Irish wolfhounds. The impaired expression of HSP90AA1 could trigger the observed differences in mRNA and protein levels and therefore explain the link between two very different functions of AHR: regulation of the closure of the ductus venosus and the response to toxins.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0057973</identifier><identifier>PMID: 23472125</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiogenesis ; Animals ; Aromatic compounds ; Biochemistry ; Biology ; Biopsy ; Bypasses ; CYP1A2 protein ; Cytochrome ; Cytochrome P-450 ; Cytochrome P450 ; Cytochromes ; Cytochromes P450 ; Cytoplasm ; Cytoplasm - metabolism ; Deoxyribonucleic acid ; Dioxins ; DNA ; Dogs ; Endothelial growth factors ; Endothelins ; Experiments ; Female ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Genes ; Genetic Linkage ; Hazardous substances ; Heat shock factors ; Heat shock proteins ; Hepatocytes ; HSP90 Heat-Shock Proteins - metabolism ; Hsp90 protein ; Hydrocarbons ; Hypoxia ; Immunohistochemistry ; Liver ; Liver - metabolism ; Localization ; Male ; Medical research ; Medicine ; Mice ; Nitric oxide ; Nuclei ; Oligonucleotide Array Sequence Analysis ; Open Reading Frames ; Pedigree ; Physiology ; Pulmonary arteries ; Receptors, Aryl Hydrocarbon - metabolism ; Repetitive Sequences, Nucleic Acid ; RNA ; RNA, Messenger - metabolism ; Rodents ; Sequence Analysis, DNA ; Shunts ; Toxins ; Vascular endothelial growth factor ; Vascularization ; Veterinary medicine</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e57973</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 van Steenbeek et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 van Steenbeek et al 2013 van Steenbeek et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-20505cc5495058f50e00a6701f8cd913c65dd6a4807c5ba051cb6354d4a430473</citedby><cites>FETCH-LOGICAL-c692t-20505cc5495058f50e00a6701f8cd913c65dd6a4807c5ba051cb6354d4a430473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589449/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589449/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23472125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Steenbeek, Frank G</creatorcontrib><creatorcontrib>Spee, Bart</creatorcontrib><creatorcontrib>Penning, Louis C</creatorcontrib><creatorcontrib>Kummeling, Anne</creatorcontrib><creatorcontrib>van Gils, Ingrid H M</creatorcontrib><creatorcontrib>Grinwis, Guy C M</creatorcontrib><creatorcontrib>Van Leenen, Dik</creatorcontrib><creatorcontrib>Holstege, Frank C P</creatorcontrib><creatorcontrib>Vos-Loohuis, Manon</creatorcontrib><creatorcontrib>Rothuizen, Jan</creatorcontrib><creatorcontrib>Leegwater, Peter A J</creatorcontrib><title>Altered subcellular localization of heat shock protein 90 is associated with impaired expression of the aryl hydrocarbon receptor pathway in dogs</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhound. We compared the expression of components of the AHR pathway in healthy Irish wolfhounds and dogs with IHPSS. To this end, we analyzed the mRNA expression in the liver of AHR,AIP, ARNT, and other genes involved in this pathway, namely, those for aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), hypoxia inducible factor 1alpha (HIF1A), heat shock protein 90AA1 (HSP90AA1), cytochromes P450 (CYP1A1, CYP1A2, and CYP1B1), vascular endothelial growth factor A (VEGFA), nitric oxide synthesase 3 (NOS3), and endothelin (EDN1). The observed low expression of AHR mRNA in the Irish wolfhounds is in associated with a LINE-1 insertion in intron 2, for which these dogs were homozygous. Down regulation in Irish wolfhounds was observed for AIP, ARNT2, CYP1A2, CYP1B1 and HSP90AA1 expression, whereas the expression of HIF1A was increased. Immunohistochemistry revealed lower levels of AHR, HIF1A, and VEGFA protein in the nucleus and lower levels of ARNT and HSP90AA1 protein in the cytoplasm of the liver cells of Irish wolfhounds. The impaired expression of HSP90AA1 could trigger the observed differences in mRNA and protein levels and therefore explain the link between two very different functions of AHR: regulation of the closure of the ductus venosus and the response to toxins.</description><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Aromatic compounds</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biopsy</subject><subject>Bypasses</subject><subject>CYP1A2 protein</subject><subject>Cytochrome</subject><subject>Cytochrome P-450</subject><subject>Cytochrome P450</subject><subject>Cytochromes</subject><subject>Cytochromes P450</subject><subject>Cytoplasm</subject><subject>Cytoplasm - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>Dioxins</subject><subject>DNA</subject><subject>Dogs</subject><subject>Endothelial growth factors</subject><subject>Endothelins</subject><subject>Experiments</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Genetic Linkage</subject><subject>Hazardous substances</subject><subject>Heat shock factors</subject><subject>Heat shock proteins</subject><subject>Hepatocytes</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Hsp90 protein</subject><subject>Hydrocarbons</subject><subject>Hypoxia</subject><subject>Immunohistochemistry</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Localization</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Nitric oxide</subject><subject>Nuclei</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Open Reading 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Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Steenbeek, Frank G</au><au>Spee, Bart</au><au>Penning, Louis C</au><au>Kummeling, Anne</au><au>van Gils, Ingrid H M</au><au>Grinwis, Guy C M</au><au>Van Leenen, Dik</au><au>Holstege, Frank C P</au><au>Vos-Loohuis, Manon</au><au>Rothuizen, Jan</au><au>Leegwater, Peter A J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered subcellular localization of heat shock protein 90 is associated with impaired expression of the aryl hydrocarbon receptor pathway in dogs</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-03-05</date><risdate>2013</risdate><volume>8</volume><issue>3</issue><spage>e57973</spage><pages>e57973-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein (AIP) and aryl hydrocarbon receptor nuclear translocator (ARNT). The resulting intrahepatic portosystemic shunts (IHPSS) are frequently diagnosed in specific dog breeds, such as the Irish wolfhound. We compared the expression of components of the AHR pathway in healthy Irish wolfhounds and dogs with IHPSS. To this end, we analyzed the mRNA expression in the liver of AHR,AIP, ARNT, and other genes involved in this pathway, namely, those for aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), hypoxia inducible factor 1alpha (HIF1A), heat shock protein 90AA1 (HSP90AA1), cytochromes P450 (CYP1A1, CYP1A2, and CYP1B1), vascular endothelial growth factor A (VEGFA), nitric oxide synthesase 3 (NOS3), and endothelin (EDN1). The observed low expression of AHR mRNA in the Irish wolfhounds is in associated with a LINE-1 insertion in intron 2, for which these dogs were homozygous. Down regulation in Irish wolfhounds was observed for AIP, ARNT2, CYP1A2, CYP1B1 and HSP90AA1 expression, whereas the expression of HIF1A was increased. Immunohistochemistry revealed lower levels of AHR, HIF1A, and VEGFA protein in the nucleus and lower levels of ARNT and HSP90AA1 protein in the cytoplasm of the liver cells of Irish wolfhounds. The impaired expression of HSP90AA1 could trigger the observed differences in mRNA and protein levels and therefore explain the link between two very different functions of AHR: regulation of the closure of the ductus venosus and the response to toxins.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23472125</pmid><doi>10.1371/journal.pone.0057973</doi><tpages>e57973</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-03, Vol.8 (3), p.e57973 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1330880763 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Angiogenesis Animals Aromatic compounds Biochemistry Biology Biopsy Bypasses CYP1A2 protein Cytochrome Cytochrome P-450 Cytochrome P450 Cytochromes Cytochromes P450 Cytoplasm Cytoplasm - metabolism Deoxyribonucleic acid Dioxins DNA Dogs Endothelial growth factors Endothelins Experiments Female Gene expression Gene Expression Profiling Gene Expression Regulation Genes Genetic Linkage Hazardous substances Heat shock factors Heat shock proteins Hepatocytes HSP90 Heat-Shock Proteins - metabolism Hsp90 protein Hydrocarbons Hypoxia Immunohistochemistry Liver Liver - metabolism Localization Male Medical research Medicine Mice Nitric oxide Nuclei Oligonucleotide Array Sequence Analysis Open Reading Frames Pedigree Physiology Pulmonary arteries Receptors, Aryl Hydrocarbon - metabolism Repetitive Sequences, Nucleic Acid RNA RNA, Messenger - metabolism Rodents Sequence Analysis, DNA Shunts Toxins Vascular endothelial growth factor Vascularization Veterinary medicine |
| title | Altered subcellular localization of heat shock protein 90 is associated with impaired expression of the aryl hydrocarbon receptor pathway in dogs |
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