Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame
•A highly conserved short open reading frame (sORF) is present in exon 2 upstream of the angiotensin (Ang II) 1a receptor (AT1aR) coding region.•This sORF has no effect on rate of AT1aR internalization.•This sORF decreases ligand potency for Ang II activation of extracellular signal-related kinases...
Gespeichert in:
| Veröffentlicht in: | Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2021-06, Vol.140, p.170529-170529, Article 170529 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 170529 |
|---|---|
| container_issue | |
| container_start_page | 170529 |
| container_title | Peptides (New York, N.Y. : 1980) |
| container_volume | 140 |
| creator | Kadam, Parnika S. Mueller, Susette C. Ji, Hong Liu, Jun Pai, Amrita V. Ma, Junfeng Speth, Robert C. Sandberg, Kathryn |
| description | •A highly conserved short open reading frame (sORF) is present in exon 2 upstream of the angiotensin (Ang II) 1a receptor (AT1aR) coding region.•This sORF has no effect on rate of AT1aR internalization.•This sORF decreases ligand potency for Ang II activation of extracellular signal-related kinases (ERK)1/2.•Inhibition of protein kinase C fully blocks Ang II-induced ERK1/2 activation.•This sORF improves cell survival.
The rat angiotensin type 1a receptor (AT1aR) is a peptide hormone G protein-coupled receptor (GPCR) that plays a key role in electrolyte homeostasis and blood pressure control. There is a highly conserved short open reading frame (sORF) in exon 2 (E2) that is downstream from exon 1 (E1) and upstream of the AT1aR coding region located in exon 3 (E3). To determine the role of this E2 sORF in AT1aR signaling, human embryonic kidney-293 (HEK293) cells were transfected with plasmids containing AT1aR cDNA with either an intact or disrupted E2 sORF. The intact sORF attenuated the efficacy of angiotensin (Ang) II (p < 0.001) and sarcosine1,Ile4,Ile8-Ang II (SII), (p < 0.01) to activate AT1aR signaling through extracellular signal-related kinases 1/2 (ERK1/2). A time-course showed agonist-induced AT1aR-mediated ERK1/2 activation was slower in the presence of the intact compared to the disrupted sORF [Ang II: p < 0.01 and SII: p < 0.05]. Ang II-induced ERK1/2 activation was completely inhibited by the protein kinase C (PKC) inhibitor Ro 31–8220 regardless of whether the sORF was intact or disrupted. Flow cytometric analyses suggested the intact sORF improved cell survival; the percentage of live cells increased (p < 0.05) while the percentage of early apoptotic cells decreased (p < 0.01) in cells transfected with the AT1aR plasmid containing the intact sORF. These findings have implications for the regulation of AT1Rs in physiological and pathological conditions and warrant investigation of sORFs in the 5′ leader sequence (5′LS) of other GPCRs. |
| doi_str_mv | 10.1016/j.peptides.2021.170529 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2503666154</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0196978121000371</els_id><sourcerecordid>2503666154</sourcerecordid><originalsourceid>FETCH-LOGICAL-c368t-e1b266856ec725b5976440198920162d980474eecd1b93e290c98a325cdd0c8c3</originalsourceid><addsrcrecordid>eNqFkD1v2zAQhomgQex8_AWDYxc5_BJFbimCtgngokuzZCEo8pzQsESFpAr434eB466dbrjn7r17EFpRsqaEytvdeoKpBA95zQija9qRlukztKSq401Lpf6CloRq2ehO0QW6zHlHCBFCqwu04LwTgku9RM-_op_3toQ44rjF5RVwsgXb8SXEAmMOIy6HCTC1OIGrkTHh_lD7eJ5ySWAHnF9jKjhOMFbE-jC-4G2yA1yj863dZ7j5rFfo6cf3P_cPzeb3z8f7b5vGcalKA7RnUqpWgutY27e6k0LUy5Vm9VHmtSKiEwDO015zYJo4rSxnrfOeOOX4Ffp63Dul-DZDLmYI2cF-b0eIczasJVxKSVtRUXlEXYo5J9iaKYXBpoOhxHx4NTtz8mo-vJqj1zq4-syY-wH8v7GTyArcHQGon_4NkEx2AUYHPlRvxfgY_pfxDnAfjFw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2503666154</pqid></control><display><type>article</type><title>Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Kadam, Parnika S. ; Mueller, Susette C. ; Ji, Hong ; Liu, Jun ; Pai, Amrita V. ; Ma, Junfeng ; Speth, Robert C. ; Sandberg, Kathryn</creator><creatorcontrib>Kadam, Parnika S. ; Mueller, Susette C. ; Ji, Hong ; Liu, Jun ; Pai, Amrita V. ; Ma, Junfeng ; Speth, Robert C. ; Sandberg, Kathryn</creatorcontrib><description><![CDATA[•A highly conserved short open reading frame (sORF) is present in exon 2 upstream of the angiotensin (Ang II) 1a receptor (AT1aR) coding region.•This sORF has no effect on rate of AT1aR internalization.•This sORF decreases ligand potency for Ang II activation of extracellular signal-related kinases (ERK)1/2.•Inhibition of protein kinase C fully blocks Ang II-induced ERK1/2 activation.•This sORF improves cell survival.
The rat angiotensin type 1a receptor (AT1aR) is a peptide hormone G protein-coupled receptor (GPCR) that plays a key role in electrolyte homeostasis and blood pressure control. There is a highly conserved short open reading frame (sORF) in exon 2 (E2) that is downstream from exon 1 (E1) and upstream of the AT1aR coding region located in exon 3 (E3). To determine the role of this E2 sORF in AT1aR signaling, human embryonic kidney-293 (HEK293) cells were transfected with plasmids containing AT1aR cDNA with either an intact or disrupted E2 sORF. The intact sORF attenuated the efficacy of angiotensin (Ang) II (p < 0.001) and sarcosine1,Ile4,Ile8-Ang II (SII), (p < 0.01) to activate AT1aR signaling through extracellular signal-related kinases 1/2 (ERK1/2). A time-course showed agonist-induced AT1aR-mediated ERK1/2 activation was slower in the presence of the intact compared to the disrupted sORF [Ang II: p < 0.01 and SII: p < 0.05]. Ang II-induced ERK1/2 activation was completely inhibited by the protein kinase C (PKC) inhibitor Ro 31–8220 regardless of whether the sORF was intact or disrupted. Flow cytometric analyses suggested the intact sORF improved cell survival; the percentage of live cells increased (p < 0.05) while the percentage of early apoptotic cells decreased (p < 0.01) in cells transfected with the AT1aR plasmid containing the intact sORF. These findings have implications for the regulation of AT1Rs in physiological and pathological conditions and warrant investigation of sORFs in the 5′ leader sequence (5′LS) of other GPCRs.]]></description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/j.peptides.2021.170529</identifier><identifier>PMID: 33744369</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Angiotensin II - metabolism ; Angiotensin II - pharmacology ; Animals ; Biased agonist ; Blood Pressure - physiology ; Cell Line ; Cell Survival - physiology ; Endocytosis ; Humans ; MAP Kinase Signaling System - drug effects ; Open Reading Frames - genetics ; PEP7 ; Phosphorylation ; Posttranscriptional regulation ; Rats ; Receptor internalization ; Receptor, Angiotensin, Type 1 - chemistry ; Receptor, Angiotensin, Type 1 - genetics ; Receptor, Angiotensin, Type 1 - metabolism ; Signal Transduction ; Transfection - methods ; β-arrestin</subject><ispartof>Peptides (New York, N.Y. : 1980), 2021-06, Vol.140, p.170529-170529, Article 170529</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c368t-e1b266856ec725b5976440198920162d980474eecd1b93e290c98a325cdd0c8c3</citedby><cites>FETCH-LOGICAL-c368t-e1b266856ec725b5976440198920162d980474eecd1b93e290c98a325cdd0c8c3</cites><orcidid>0000-0003-2967-8336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.peptides.2021.170529$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33744369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kadam, Parnika S.</creatorcontrib><creatorcontrib>Mueller, Susette C.</creatorcontrib><creatorcontrib>Ji, Hong</creatorcontrib><creatorcontrib>Liu, Jun</creatorcontrib><creatorcontrib>Pai, Amrita V.</creatorcontrib><creatorcontrib>Ma, Junfeng</creatorcontrib><creatorcontrib>Speth, Robert C.</creatorcontrib><creatorcontrib>Sandberg, Kathryn</creatorcontrib><title>Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame</title><title>Peptides (New York, N.Y. : 1980)</title><addtitle>Peptides</addtitle><description><![CDATA[•A highly conserved short open reading frame (sORF) is present in exon 2 upstream of the angiotensin (Ang II) 1a receptor (AT1aR) coding region.•This sORF has no effect on rate of AT1aR internalization.•This sORF decreases ligand potency for Ang II activation of extracellular signal-related kinases (ERK)1/2.•Inhibition of protein kinase C fully blocks Ang II-induced ERK1/2 activation.•This sORF improves cell survival.
The rat angiotensin type 1a receptor (AT1aR) is a peptide hormone G protein-coupled receptor (GPCR) that plays a key role in electrolyte homeostasis and blood pressure control. There is a highly conserved short open reading frame (sORF) in exon 2 (E2) that is downstream from exon 1 (E1) and upstream of the AT1aR coding region located in exon 3 (E3). To determine the role of this E2 sORF in AT1aR signaling, human embryonic kidney-293 (HEK293) cells were transfected with plasmids containing AT1aR cDNA with either an intact or disrupted E2 sORF. The intact sORF attenuated the efficacy of angiotensin (Ang) II (p < 0.001) and sarcosine1,Ile4,Ile8-Ang II (SII), (p < 0.01) to activate AT1aR signaling through extracellular signal-related kinases 1/2 (ERK1/2). A time-course showed agonist-induced AT1aR-mediated ERK1/2 activation was slower in the presence of the intact compared to the disrupted sORF [Ang II: p < 0.01 and SII: p < 0.05]. Ang II-induced ERK1/2 activation was completely inhibited by the protein kinase C (PKC) inhibitor Ro 31–8220 regardless of whether the sORF was intact or disrupted. Flow cytometric analyses suggested the intact sORF improved cell survival; the percentage of live cells increased (p < 0.05) while the percentage of early apoptotic cells decreased (p < 0.01) in cells transfected with the AT1aR plasmid containing the intact sORF. These findings have implications for the regulation of AT1Rs in physiological and pathological conditions and warrant investigation of sORFs in the 5′ leader sequence (5′LS) of other GPCRs.]]></description><subject>Angiotensin II - metabolism</subject><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Biased agonist</subject><subject>Blood Pressure - physiology</subject><subject>Cell Line</subject><subject>Cell Survival - physiology</subject><subject>Endocytosis</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Open Reading Frames - genetics</subject><subject>PEP7</subject><subject>Phosphorylation</subject><subject>Posttranscriptional regulation</subject><subject>Rats</subject><subject>Receptor internalization</subject><subject>Receptor, Angiotensin, Type 1 - chemistry</subject><subject>Receptor, Angiotensin, Type 1 - genetics</subject><subject>Receptor, Angiotensin, Type 1 - metabolism</subject><subject>Signal Transduction</subject><subject>Transfection - methods</subject><subject>β-arrestin</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD1v2zAQhomgQex8_AWDYxc5_BJFbimCtgngokuzZCEo8pzQsESFpAr434eB466dbrjn7r17EFpRsqaEytvdeoKpBA95zQija9qRlukztKSq401Lpf6CloRq2ehO0QW6zHlHCBFCqwu04LwTgku9RM-_op_3toQ44rjF5RVwsgXb8SXEAmMOIy6HCTC1OIGrkTHh_lD7eJ5ySWAHnF9jKjhOMFbE-jC-4G2yA1yj863dZ7j5rFfo6cf3P_cPzeb3z8f7b5vGcalKA7RnUqpWgutY27e6k0LUy5Vm9VHmtSKiEwDO015zYJo4rSxnrfOeOOX4Ffp63Dul-DZDLmYI2cF-b0eIczasJVxKSVtRUXlEXYo5J9iaKYXBpoOhxHx4NTtz8mo-vJqj1zq4-syY-wH8v7GTyArcHQGon_4NkEx2AUYHPlRvxfgY_pfxDnAfjFw</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Kadam, Parnika S.</creator><creator>Mueller, Susette C.</creator><creator>Ji, Hong</creator><creator>Liu, Jun</creator><creator>Pai, Amrita V.</creator><creator>Ma, Junfeng</creator><creator>Speth, Robert C.</creator><creator>Sandberg, Kathryn</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><orcidid>https://orcid.org/0000-0003-2967-8336</orcidid></search><sort><creationdate>202106</creationdate><title>Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame</title><author>Kadam, Parnika S. ; Mueller, Susette C. ; Ji, Hong ; Liu, Jun ; Pai, Amrita V. ; Ma, Junfeng ; Speth, Robert C. ; Sandberg, Kathryn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c368t-e1b266856ec725b5976440198920162d980474eecd1b93e290c98a325cdd0c8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiotensin II - metabolism</topic><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Biased agonist</topic><topic>Blood Pressure - physiology</topic><topic>Cell Line</topic><topic>Cell Survival - physiology</topic><topic>Endocytosis</topic><topic>Humans</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Open Reading Frames - genetics</topic><topic>PEP7</topic><topic>Phosphorylation</topic><topic>Posttranscriptional regulation</topic><topic>Rats</topic><topic>Receptor internalization</topic><topic>Receptor, Angiotensin, Type 1 - chemistry</topic><topic>Receptor, Angiotensin, Type 1 - genetics</topic><topic>Receptor, Angiotensin, Type 1 - metabolism</topic><topic>Signal Transduction</topic><topic>Transfection - methods</topic><topic>β-arrestin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kadam, Parnika S.</creatorcontrib><creatorcontrib>Mueller, Susette C.</creatorcontrib><creatorcontrib>Ji, Hong</creatorcontrib><creatorcontrib>Liu, Jun</creatorcontrib><creatorcontrib>Pai, Amrita V.</creatorcontrib><creatorcontrib>Ma, Junfeng</creatorcontrib><creatorcontrib>Speth, Robert C.</creatorcontrib><creatorcontrib>Sandberg, Kathryn</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>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kadam, Parnika S.</au><au>Mueller, Susette C.</au><au>Ji, Hong</au><au>Liu, Jun</au><au>Pai, Amrita V.</au><au>Ma, Junfeng</au><au>Speth, Robert C.</au><au>Sandberg, Kathryn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>2021-06</date><risdate>2021</risdate><volume>140</volume><spage>170529</spage><epage>170529</epage><pages>170529-170529</pages><artnum>170529</artnum><issn>0196-9781</issn><eissn>1873-5169</eissn><abstract><![CDATA[•A highly conserved short open reading frame (sORF) is present in exon 2 upstream of the angiotensin (Ang II) 1a receptor (AT1aR) coding region.•This sORF has no effect on rate of AT1aR internalization.•This sORF decreases ligand potency for Ang II activation of extracellular signal-related kinases (ERK)1/2.•Inhibition of protein kinase C fully blocks Ang II-induced ERK1/2 activation.•This sORF improves cell survival.
The rat angiotensin type 1a receptor (AT1aR) is a peptide hormone G protein-coupled receptor (GPCR) that plays a key role in electrolyte homeostasis and blood pressure control. There is a highly conserved short open reading frame (sORF) in exon 2 (E2) that is downstream from exon 1 (E1) and upstream of the AT1aR coding region located in exon 3 (E3). To determine the role of this E2 sORF in AT1aR signaling, human embryonic kidney-293 (HEK293) cells were transfected with plasmids containing AT1aR cDNA with either an intact or disrupted E2 sORF. The intact sORF attenuated the efficacy of angiotensin (Ang) II (p < 0.001) and sarcosine1,Ile4,Ile8-Ang II (SII), (p < 0.01) to activate AT1aR signaling through extracellular signal-related kinases 1/2 (ERK1/2). A time-course showed agonist-induced AT1aR-mediated ERK1/2 activation was slower in the presence of the intact compared to the disrupted sORF [Ang II: p < 0.01 and SII: p < 0.05]. Ang II-induced ERK1/2 activation was completely inhibited by the protein kinase C (PKC) inhibitor Ro 31–8220 regardless of whether the sORF was intact or disrupted. Flow cytometric analyses suggested the intact sORF improved cell survival; the percentage of live cells increased (p < 0.05) while the percentage of early apoptotic cells decreased (p < 0.01) in cells transfected with the AT1aR plasmid containing the intact sORF. These findings have implications for the regulation of AT1Rs in physiological and pathological conditions and warrant investigation of sORFs in the 5′ leader sequence (5′LS) of other GPCRs.]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33744369</pmid><doi>10.1016/j.peptides.2021.170529</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2967-8336</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0196-9781 |
| ispartof | Peptides (New York, N.Y. : 1980), 2021-06, Vol.140, p.170529-170529, Article 170529 |
| issn | 0196-9781 1873-5169 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2503666154 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Angiotensin II - metabolism Angiotensin II - pharmacology Animals Biased agonist Blood Pressure - physiology Cell Line Cell Survival - physiology Endocytosis Humans MAP Kinase Signaling System - drug effects Open Reading Frames - genetics PEP7 Phosphorylation Posttranscriptional regulation Rats Receptor internalization Receptor, Angiotensin, Type 1 - chemistry Receptor, Angiotensin, Type 1 - genetics Receptor, Angiotensin, Type 1 - metabolism Signal Transduction Transfection - methods β-arrestin |
| title | Modulation of the rat angiotensin type 1a receptor by an upstream short open reading frame |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T00%3A35%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Modulation%20of%20the%20rat%20angiotensin%20type%201a%20receptor%20by%20an%20upstream%20short%20open%20reading%20frame&rft.jtitle=Peptides%20(New%20York,%20N.Y.%20:%201980)&rft.au=Kadam,%20Parnika%20S.&rft.date=2021-06&rft.volume=140&rft.spage=170529&rft.epage=170529&rft.pages=170529-170529&rft.artnum=170529&rft.issn=0196-9781&rft.eissn=1873-5169&rft_id=info:doi/10.1016/j.peptides.2021.170529&rft_dat=%3Cproquest_cross%3E2503666154%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2503666154&rft_id=info:pmid/33744369&rft_els_id=S0196978121000371&rfr_iscdi=true |