Expression of β-Arrestins and β-Adrenergic Receptor Kinases in the Failing Human Heart
The β-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in β-adrenergic receptor kinase (βARK) expression. βARK is thought to effect desensitization by acting in concert with an i...
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| Veröffentlicht in: | Circulation research 1994-02, Vol.74 (2), p.206-213 |
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| creator | Ungerer, Martin Parruti, Giustino Böhm, Michael Puzicha, Mechthild DeBlasi, Antonio Erdmann, Erland Lohse, Martin J |
| description | The β-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in β-adrenergic receptor kinase (βARK) expression. βARK is thought to effect desensitization by acting in concert with an inhibitor protein, called β-arrestin. Two isoforms have been identified both for βARK and for β-arrestin. In the present study, we have investigated the expression of the individual isoforms of β-arrestin and of βARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, β-arrestin-1, β-arrestin-2, βARK-1, and βARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for β-arrestin-1 and β-arrestin-2, a slight ( |
| doi_str_mv | 10.1161/01.res.74.2.206 |
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We have recently postulated that this desensitization may in part be caused by an increase in β-adrenergic receptor kinase (βARK) expression. βARK is thought to effect desensitization by acting in concert with an inhibitor protein, called β-arrestin. Two isoforms have been identified both for βARK and for β-arrestin. In the present study, we have investigated the expression of the individual isoforms of β-arrestin and of βARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, β-arrestin-1, β-arrestin-2, βARK-1, and βARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for β-arrestin-1 and β-arrestin-2, a slight (<50%) increase of the mRNA for βARK-2, and a threefold increase for βARK-1 mRNA. At the protein level, β-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were ≈350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. β-Arrestin-2 levels were too low to be detectable using the same methods. βARK levels as determined by enzymatic activity were ≈20 fmol/mg cytosolic protein (βARK-1 plus βARK-2) and thus almost 20-fold lower than those of β-arrestin. βARK levels were increased approximately twofold in heart failure. We hypothesize that, because of its low expression, βARK may be the limiting component in β-adrenergic receptor desensitization in the human heart and that upregulation of βARK-1 expression in heart failure may, therefore, play a major role in the desensitization of these receptors.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.res.74.2.206</identifier><identifier>PMID: 8293560</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adult ; Aged ; Amino Acid Sequence ; Antigens - genetics ; Antigens - metabolism ; Arrestins ; beta-Adrenergic Receptor Kinases ; beta-Arrestin 1 ; beta-Arrestin 2 ; beta-Arrestins ; Biological and medical sciences ; Blotting, Western ; Cardiac Output, Low - metabolism ; Cardiology. Vascular system ; Cyclic AMP-Dependent Protein Kinases - genetics ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Eye Proteins - genetics ; Eye Proteins - metabolism ; Female ; Heart ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Humans ; Isomerism ; Male ; Medical sciences ; Middle Aged ; Molecular Sequence Data ; Myocardium - metabolism ; Peptide Fragments - genetics ; Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Transcription, Genetic</subject><ispartof>Circulation research, 1994-02, Vol.74 (2), p.206-213</ispartof><rights>1994 American Heart Association, Inc.</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5555-8925759481ef7ce2ebe62971f5222ce6fa6d85b01fa604373a353cfec792307d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3922208$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8293560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ungerer, Martin</creatorcontrib><creatorcontrib>Parruti, Giustino</creatorcontrib><creatorcontrib>Böhm, Michael</creatorcontrib><creatorcontrib>Puzicha, Mechthild</creatorcontrib><creatorcontrib>DeBlasi, Antonio</creatorcontrib><creatorcontrib>Erdmann, Erland</creatorcontrib><creatorcontrib>Lohse, Martin J</creatorcontrib><title>Expression of β-Arrestins and β-Adrenergic Receptor Kinases in the Failing Human Heart</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>The β-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in β-adrenergic receptor kinase (βARK) expression. βARK is thought to effect desensitization by acting in concert with an inhibitor protein, called β-arrestin. Two isoforms have been identified both for βARK and for β-arrestin. In the present study, we have investigated the expression of the individual isoforms of β-arrestin and of βARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, β-arrestin-1, β-arrestin-2, βARK-1, and βARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for β-arrestin-1 and β-arrestin-2, a slight (<50%) increase of the mRNA for βARK-2, and a threefold increase for βARK-1 mRNA. At the protein level, β-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were ≈350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. β-Arrestin-2 levels were too low to be detectable using the same methods. βARK levels as determined by enzymatic activity were ≈20 fmol/mg cytosolic protein (βARK-1 plus βARK-2) and thus almost 20-fold lower than those of β-arrestin. βARK levels were increased approximately twofold in heart failure. We hypothesize that, because of its low expression, βARK may be the limiting component in β-adrenergic receptor desensitization in the human heart and that upregulation of βARK-1 expression in heart failure may, therefore, play a major role in the desensitization of these receptors.</description><subject>Adult</subject><subject>Aged</subject><subject>Amino Acid Sequence</subject><subject>Antigens - genetics</subject><subject>Antigens - metabolism</subject><subject>Arrestins</subject><subject>beta-Adrenergic Receptor Kinases</subject><subject>beta-Arrestin 1</subject><subject>beta-Arrestin 2</subject><subject>beta-Arrestins</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cardiac Output, Low - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cyclic AMP-Dependent Protein Kinases - genetics</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Eye Proteins - genetics</subject><subject>Eye Proteins - metabolism</subject><subject>Female</subject><subject>Heart</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Humans</subject><subject>Isomerism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Myocardium - metabolism</subject><subject>Peptide Fragments - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription, Genetic</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kc9u1DAQxi0EKtuFMyckHxC3pON_cXysqi1bUQmpLRI3y-tMuoass9iJCq_VB-kz4bKr-jD2zPz8jfWZkA8MasYadgasTphrLWtec2hekQVTXFZSafaaLADAVFoIeEtOc_4JwKTg5oSctNwI1cCC_Fj92ReBHMZIx54-PVbnqeRTiJm62P0vdAkjpvvg6Q163E9jol9DdBkzDZFOW6SXLgwh3tP1vHORrtGl6R1507sh4_vjviTfL1d3F-vq-tuXq4vz68qrsqrWcKWVkS3DXnvkuMGGG816xTn32PSu6Vq1AVYOIIUWTijhe_TacAG6E0vy-aC7T-Pvubzc7kL2OAwu4jhnqxshDC9hSc4OoE9jzgl7u09h59Jfy8A-e2mB2ZvVrdXSclu8LDc-HqXnzQ67F_5oXul_OvZd9m7ok4s-5BesjOUc2oLJA_YwDhOm_GuYHzDZLbph2tryRSCA8YoZI4GXrHouKfEP472MJg</recordid><startdate>199402</startdate><enddate>199402</enddate><creator>Ungerer, Martin</creator><creator>Parruti, Giustino</creator><creator>Böhm, Michael</creator><creator>Puzicha, Mechthild</creator><creator>DeBlasi, Antonio</creator><creator>Erdmann, Erland</creator><creator>Lohse, Martin J</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</scope><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>199402</creationdate><title>Expression of β-Arrestins and β-Adrenergic Receptor Kinases in the Failing Human Heart</title><author>Ungerer, Martin ; Parruti, Giustino ; Böhm, Michael ; Puzicha, Mechthild ; DeBlasi, Antonio ; Erdmann, Erland ; Lohse, Martin J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5555-8925759481ef7ce2ebe62971f5222ce6fa6d85b01fa604373a353cfec792307d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Amino Acid Sequence</topic><topic>Antigens - genetics</topic><topic>Antigens - metabolism</topic><topic>Arrestins</topic><topic>beta-Adrenergic Receptor Kinases</topic><topic>beta-Arrestin 1</topic><topic>beta-Arrestin 2</topic><topic>beta-Arrestins</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cardiac Output, Low - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Cyclic AMP-Dependent Protein Kinases - genetics</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Eye Proteins - genetics</topic><topic>Eye Proteins - metabolism</topic><topic>Female</topic><topic>Heart</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Humans</topic><topic>Isomerism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Myocardium - metabolism</topic><topic>Peptide Fragments - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ungerer, Martin</creatorcontrib><creatorcontrib>Parruti, Giustino</creatorcontrib><creatorcontrib>Böhm, Michael</creatorcontrib><creatorcontrib>Puzicha, Mechthild</creatorcontrib><creatorcontrib>DeBlasi, Antonio</creatorcontrib><creatorcontrib>Erdmann, Erland</creatorcontrib><creatorcontrib>Lohse, Martin J</creatorcontrib><collection>Pascal-Francis</collection><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>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ungerer, Martin</au><au>Parruti, Giustino</au><au>Böhm, Michael</au><au>Puzicha, Mechthild</au><au>DeBlasi, Antonio</au><au>Erdmann, Erland</au><au>Lohse, Martin J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of β-Arrestins and β-Adrenergic Receptor Kinases in the Failing Human Heart</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>1994-02</date><risdate>1994</risdate><volume>74</volume><issue>2</issue><spage>206</spage><epage>213</epage><pages>206-213</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>The β-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in β-adrenergic receptor kinase (βARK) expression. βARK is thought to effect desensitization by acting in concert with an inhibitor protein, called β-arrestin. Two isoforms have been identified both for βARK and for β-arrestin. In the present study, we have investigated the expression of the individual isoforms of β-arrestin and of βARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, β-arrestin-1, β-arrestin-2, βARK-1, and βARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for β-arrestin-1 and β-arrestin-2, a slight (<50%) increase of the mRNA for βARK-2, and a threefold increase for βARK-1 mRNA. At the protein level, β-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were ≈350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. β-Arrestin-2 levels were too low to be detectable using the same methods. βARK levels as determined by enzymatic activity were ≈20 fmol/mg cytosolic protein (βARK-1 plus βARK-2) and thus almost 20-fold lower than those of β-arrestin. βARK levels were increased approximately twofold in heart failure. We hypothesize that, because of its low expression, βARK may be the limiting component in β-adrenergic receptor desensitization in the human heart and that upregulation of βARK-1 expression in heart failure may, therefore, play a major role in the desensitization of these receptors.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>8293560</pmid><doi>10.1161/01.res.74.2.206</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation research, 1994-02, Vol.74 (2), p.206-213 |
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| language | eng |
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| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete |
| subjects | Adult Aged Amino Acid Sequence Antigens - genetics Antigens - metabolism Arrestins beta-Adrenergic Receptor Kinases beta-Arrestin 1 beta-Arrestin 2 beta-Arrestins Biological and medical sciences Blotting, Western Cardiac Output, Low - metabolism Cardiology. Vascular system Cyclic AMP-Dependent Protein Kinases - genetics Cyclic AMP-Dependent Protein Kinases - metabolism Eye Proteins - genetics Eye Proteins - metabolism Female Heart Heart failure, cardiogenic pulmonary edema, cardiac enlargement Humans Isomerism Male Medical sciences Middle Aged Molecular Sequence Data Myocardium - metabolism Peptide Fragments - genetics Polymerase Chain Reaction RNA, Messenger - metabolism Transcription, Genetic |
| title | Expression of β-Arrestins and β-Adrenergic Receptor Kinases in the Failing Human Heart |
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