Phosphoproteomic studies of alamandine signaling in CHO‐MrgD and human pancreatic carcinoma cells: An antiproliferative effect is unveiled
Alamandine is a heptapeptide from the renin‐angiotensin system (RAS) with similar structure/function to angiotensin‐(1‐7) [ang‐(1‐7)], but they act via different receptors. It remains elusive whether alamandine is an antiproliferative agent like ang‐(1‐7). The goal of this study was to evaluate the...
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| Veröffentlicht in: | Proteomics (Weinheim) 2022-09, Vol.22 (17), p.e2100255-n/a |
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| creator | da Silva, Filipe Alex Rodrigues‐Ribeiro, Lucas Melo‐Braga, Marcella Nunes Passos‐Silva, Danielle Gomes Sampaio, Walkyria Oliveira Gorshkov, Vladimir Kjeldsen, Frank Verano‐Braga, Thiago Santos, Robson Augusto Souza |
| description | Alamandine is a heptapeptide from the renin‐angiotensin system (RAS) with similar structure/function to angiotensin‐(1‐7) [ang‐(1‐7)], but they act via different receptors. It remains elusive whether alamandine is an antiproliferative agent like ang‐(1‐7). The goal of this study was to evaluate the potential antiproliferative activity of alamandine and the underlying cellular signaling. We evaluated alamandine effect in the tumoral cell lines Mia PaCa‐2 and A549, and in the nontumoral cell lines HaCaT, CHO and CHO transfected with the alamandine receptor MrgD (CHO‐MrgD). Alamandine was able to reduce the proliferation of the tumoral cell lines in a MrgD‐dependent fashion. We did not observe any effect in the nontumoral cell lines tested. We also performed proteomics and phosphoproteomics to study the alamandine signaling in Mia PaCa‐2 and CHO‐MrgD. Data suggest that alamandine induces a shift from anaerobic to aerobic metabolism in the tumoral cells, induces a negative regulation of PI3K/AKT/mTOR pathway and activates the transcriptional factor FoxO1; events that could explain, at least partially, the observed antiproliferative effect of alamandine. This study provides for the first time a comprehensive investigation of the alamandine signaling in tumoral (Mia PaCa‐2) and nontumoral (CHO‐MrgD) cells, highlighting the antiproliferative activity of alamandine/MrgD and its possible antitumoral effect. |
| doi_str_mv | 10.1002/pmic.202100255 |
| format | Article |
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It remains elusive whether alamandine is an antiproliferative agent like ang‐(1‐7). The goal of this study was to evaluate the potential antiproliferative activity of alamandine and the underlying cellular signaling. We evaluated alamandine effect in the tumoral cell lines Mia PaCa‐2 and A549, and in the nontumoral cell lines HaCaT, CHO and CHO transfected with the alamandine receptor MrgD (CHO‐MrgD). Alamandine was able to reduce the proliferation of the tumoral cell lines in a MrgD‐dependent fashion. We did not observe any effect in the nontumoral cell lines tested. We also performed proteomics and phosphoproteomics to study the alamandine signaling in Mia PaCa‐2 and CHO‐MrgD. Data suggest that alamandine induces a shift from anaerobic to aerobic metabolism in the tumoral cells, induces a negative regulation of PI3K/AKT/mTOR pathway and activates the transcriptional factor FoxO1; events that could explain, at least partially, the observed antiproliferative effect of alamandine. This study provides for the first time a comprehensive investigation of the alamandine signaling in tumoral (Mia PaCa‐2) and nontumoral (CHO‐MrgD) cells, highlighting the antiproliferative activity of alamandine/MrgD and its possible antitumoral effect.</description><identifier>ISSN: 1615-9853</identifier><identifier>EISSN: 1615-9861</identifier><identifier>DOI: 10.1002/pmic.202100255</identifier><identifier>PMID: 35652611</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; alamandine ; Angiotensin ; Anticancer properties ; Antiproliferatives ; cancer ; FOXO1 protein ; Humans ; Oligopeptides - metabolism ; Oligopeptides - pharmacology ; Pancreatic cancer ; Pancreatic carcinoma ; Pancreatic Neoplasms ; Phosphatidylinositol 3-Kinases ; phosphoproteomics ; Proteomics ; Receptors ; Receptors, G-Protein-Coupled - metabolism ; Renin ; renin‐angiotensin system ; Signaling ; Structure-function relationships ; TOR protein ; tumor</subject><ispartof>Proteomics (Weinheim), 2022-09, Vol.22 (17), p.e2100255-n/a</ispartof><rights>2022 Wiley‐VCH GmbH.</rights><rights>2022 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4095-44ec51e5e735047b6fef54bc16812d2b622cd54c74f5c89e05b1ddf543f997e53</citedby><cites>FETCH-LOGICAL-c4095-44ec51e5e735047b6fef54bc16812d2b622cd54c74f5c89e05b1ddf543f997e53</cites><orcidid>0000-0002-7083-2588</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpmic.202100255$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpmic.202100255$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35652611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>da Silva, Filipe Alex</creatorcontrib><creatorcontrib>Rodrigues‐Ribeiro, Lucas</creatorcontrib><creatorcontrib>Melo‐Braga, Marcella Nunes</creatorcontrib><creatorcontrib>Passos‐Silva, Danielle Gomes</creatorcontrib><creatorcontrib>Sampaio, Walkyria Oliveira</creatorcontrib><creatorcontrib>Gorshkov, Vladimir</creatorcontrib><creatorcontrib>Kjeldsen, Frank</creatorcontrib><creatorcontrib>Verano‐Braga, Thiago</creatorcontrib><creatorcontrib>Santos, Robson Augusto Souza</creatorcontrib><title>Phosphoproteomic studies of alamandine signaling in CHO‐MrgD and human pancreatic carcinoma cells: An antiproliferative effect is unveiled</title><title>Proteomics (Weinheim)</title><addtitle>Proteomics</addtitle><description>Alamandine is a heptapeptide from the renin‐angiotensin system (RAS) with similar structure/function to angiotensin‐(1‐7) [ang‐(1‐7)], but they act via different receptors. It remains elusive whether alamandine is an antiproliferative agent like ang‐(1‐7). The goal of this study was to evaluate the potential antiproliferative activity of alamandine and the underlying cellular signaling. We evaluated alamandine effect in the tumoral cell lines Mia PaCa‐2 and A549, and in the nontumoral cell lines HaCaT, CHO and CHO transfected with the alamandine receptor MrgD (CHO‐MrgD). Alamandine was able to reduce the proliferation of the tumoral cell lines in a MrgD‐dependent fashion. We did not observe any effect in the nontumoral cell lines tested. We also performed proteomics and phosphoproteomics to study the alamandine signaling in Mia PaCa‐2 and CHO‐MrgD. Data suggest that alamandine induces a shift from anaerobic to aerobic metabolism in the tumoral cells, induces a negative regulation of PI3K/AKT/mTOR pathway and activates the transcriptional factor FoxO1; events that could explain, at least partially, the observed antiproliferative effect of alamandine. This study provides for the first time a comprehensive investigation of the alamandine signaling in tumoral (Mia PaCa‐2) and nontumoral (CHO‐MrgD) cells, highlighting the antiproliferative activity of alamandine/MrgD and its possible antitumoral effect.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>alamandine</subject><subject>Angiotensin</subject><subject>Anticancer properties</subject><subject>Antiproliferatives</subject><subject>cancer</subject><subject>FOXO1 protein</subject><subject>Humans</subject><subject>Oligopeptides - metabolism</subject><subject>Oligopeptides - pharmacology</subject><subject>Pancreatic cancer</subject><subject>Pancreatic carcinoma</subject><subject>Pancreatic Neoplasms</subject><subject>Phosphatidylinositol 3-Kinases</subject><subject>phosphoproteomics</subject><subject>Proteomics</subject><subject>Receptors</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Renin</subject><subject>renin‐angiotensin system</subject><subject>Signaling</subject><subject>Structure-function relationships</subject><subject>TOR protein</subject><subject>tumor</subject><issn>1615-9853</issn><issn>1615-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkTFv1DAUxy0EoqWwMiJLLCx32E6enbBVR6GVWrUDzJHjPN-5SuxgJ6269QMw8Bn7SerTlRu6VB5syz__3tP7E_KRsyVnTHwdB2eWgontBeAVOeSSw6KuJH-9P0NxQN6ldM0YV1Wt3pKDAiQIyfkh-Xu1CWnchDGGCUOW0TTNncNEg6W614P2nfNIk1t73Tu_ps7T1enlw_2_i7j-TvMz3cyZoqP2JqKessLoaJwPg6YG-z59o8c-g5PLRXpnMWboBilai2aiLtHZ36DrsXtP3ljdJ_zwtB-R3z9Ofq1OF-eXP89Wx-cLU7IaFmWJBjgCqgJYqVpp0ULZGi4rLjrRSiFMB6VRpQVT1cig5V2XkcLWtUIojsiXnTc39GfGNDWDS9tWtccwp0ZIJRSTZVFn9PMz9DrMMY8iU4rVigtZFZla7igTQ0oRbTNGN-h413DWbKNptjk1-5zyh09P2rkdsNvj_4PJAOyA2zyYuxd0zdXF2YoXkNcjmlahAA</recordid><startdate>202209</startdate><enddate>202209</enddate><creator>da Silva, Filipe Alex</creator><creator>Rodrigues‐Ribeiro, Lucas</creator><creator>Melo‐Braga, Marcella Nunes</creator><creator>Passos‐Silva, Danielle Gomes</creator><creator>Sampaio, Walkyria Oliveira</creator><creator>Gorshkov, Vladimir</creator><creator>Kjeldsen, Frank</creator><creator>Verano‐Braga, Thiago</creator><creator>Santos, Robson Augusto Souza</creator><general>Wiley Subscription Services, 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>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7083-2588</orcidid></search><sort><creationdate>202209</creationdate><title>Phosphoproteomic studies of alamandine signaling in CHO‐MrgD and human pancreatic carcinoma cells: An antiproliferative effect is unveiled</title><author>da Silva, Filipe Alex ; Rodrigues‐Ribeiro, Lucas ; Melo‐Braga, Marcella Nunes ; Passos‐Silva, Danielle Gomes ; Sampaio, Walkyria Oliveira ; Gorshkov, Vladimir ; Kjeldsen, Frank ; Verano‐Braga, Thiago ; Santos, Robson Augusto Souza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4095-44ec51e5e735047b6fef54bc16812d2b622cd54c74f5c89e05b1ddf543f997e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>alamandine</topic><topic>Angiotensin</topic><topic>Anticancer properties</topic><topic>Antiproliferatives</topic><topic>cancer</topic><topic>FOXO1 protein</topic><topic>Humans</topic><topic>Oligopeptides - metabolism</topic><topic>Oligopeptides - pharmacology</topic><topic>Pancreatic cancer</topic><topic>Pancreatic carcinoma</topic><topic>Pancreatic Neoplasms</topic><topic>Phosphatidylinositol 3-Kinases</topic><topic>phosphoproteomics</topic><topic>Proteomics</topic><topic>Receptors</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Renin</topic><topic>renin‐angiotensin system</topic><topic>Signaling</topic><topic>Structure-function relationships</topic><topic>TOR protein</topic><topic>tumor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>da Silva, Filipe Alex</creatorcontrib><creatorcontrib>Rodrigues‐Ribeiro, Lucas</creatorcontrib><creatorcontrib>Melo‐Braga, Marcella Nunes</creatorcontrib><creatorcontrib>Passos‐Silva, Danielle Gomes</creatorcontrib><creatorcontrib>Sampaio, Walkyria Oliveira</creatorcontrib><creatorcontrib>Gorshkov, Vladimir</creatorcontrib><creatorcontrib>Kjeldsen, Frank</creatorcontrib><creatorcontrib>Verano‐Braga, Thiago</creatorcontrib><creatorcontrib>Santos, Robson Augusto Souza</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Proteomics (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>da Silva, Filipe Alex</au><au>Rodrigues‐Ribeiro, Lucas</au><au>Melo‐Braga, Marcella Nunes</au><au>Passos‐Silva, Danielle Gomes</au><au>Sampaio, Walkyria Oliveira</au><au>Gorshkov, Vladimir</au><au>Kjeldsen, Frank</au><au>Verano‐Braga, Thiago</au><au>Santos, Robson Augusto Souza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphoproteomic studies of alamandine signaling in CHO‐MrgD and human pancreatic carcinoma cells: An antiproliferative effect is unveiled</atitle><jtitle>Proteomics (Weinheim)</jtitle><addtitle>Proteomics</addtitle><date>2022-09</date><risdate>2022</risdate><volume>22</volume><issue>17</issue><spage>e2100255</spage><epage>n/a</epage><pages>e2100255-n/a</pages><issn>1615-9853</issn><eissn>1615-9861</eissn><abstract>Alamandine is a heptapeptide from the renin‐angiotensin system (RAS) with similar structure/function to angiotensin‐(1‐7) [ang‐(1‐7)], but they act via different receptors. It remains elusive whether alamandine is an antiproliferative agent like ang‐(1‐7). The goal of this study was to evaluate the potential antiproliferative activity of alamandine and the underlying cellular signaling. We evaluated alamandine effect in the tumoral cell lines Mia PaCa‐2 and A549, and in the nontumoral cell lines HaCaT, CHO and CHO transfected with the alamandine receptor MrgD (CHO‐MrgD). Alamandine was able to reduce the proliferation of the tumoral cell lines in a MrgD‐dependent fashion. We did not observe any effect in the nontumoral cell lines tested. We also performed proteomics and phosphoproteomics to study the alamandine signaling in Mia PaCa‐2 and CHO‐MrgD. Data suggest that alamandine induces a shift from anaerobic to aerobic metabolism in the tumoral cells, induces a negative regulation of PI3K/AKT/mTOR pathway and activates the transcriptional factor FoxO1; events that could explain, at least partially, the observed antiproliferative effect of alamandine. This study provides for the first time a comprehensive investigation of the alamandine signaling in tumoral (Mia PaCa‐2) and nontumoral (CHO‐MrgD) cells, highlighting the antiproliferative activity of alamandine/MrgD and its possible antitumoral effect.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35652611</pmid><doi>10.1002/pmic.202100255</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7083-2588</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein alamandine Angiotensin Anticancer properties Antiproliferatives cancer FOXO1 protein Humans Oligopeptides - metabolism Oligopeptides - pharmacology Pancreatic cancer Pancreatic carcinoma Pancreatic Neoplasms Phosphatidylinositol 3-Kinases phosphoproteomics Proteomics Receptors Receptors, G-Protein-Coupled - metabolism Renin renin‐angiotensin system Signaling Structure-function relationships TOR protein tumor |
| title | Phosphoproteomic studies of alamandine signaling in CHO‐MrgD and human pancreatic carcinoma cells: An antiproliferative effect is unveiled |
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