Acidification Prevents Endothelial Cell Apoptosis by Axl Activation
ABSTRACT—Prior studies have shown that acidification due to hypercarbia protects endothelial cells from serum deprivation–induced apoptosis. However, the mechanism(s) responsible for the antiapoptotic effect of acidification is still unclear. cDNA array screening was performed on human umbilical vei...
Gespeichert in:
| Veröffentlicht in: | Circulation research 2002-10, Vol.91 (7), p.e4-e12 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e12 |
|---|---|
| container_issue | 7 |
| container_start_page | e4 |
| container_title | Circulation research |
| container_volume | 91 |
| creator | D’Arcangelo, Daniela Gaetano, Carlo Capogrossi, Maurizio C |
| description | ABSTRACT—Prior studies have shown that acidification due to hypercarbia protects endothelial cells from serum deprivation–induced apoptosis. However, the mechanism(s) responsible for the antiapoptotic effect of acidification is still unclear. cDNA array screening was performed on human umbilical vein endothelial cells cultured in a bicarbonate medium equilibrated either with 5% CO2 (pH 7.4) or with 20% CO2 (pH 7.0). Tyrosine kinase receptor Axl expression was 3.3-fold higher after 6 hours at pH 7.0 compared with pH 7.4; this modulation was confirmed by reverse transcriptase–polymerase chain reaction (3.0±0.9-fold, P |
| doi_str_mv | 10.1161/01.RES.0000036753.50601.E9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72144846</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72144846</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5975-aa0f0c5ebdfab318c2395a26a12a7123a0475e31cee2c2774814a509f9f354f43</originalsourceid><addsrcrecordid>eNpdkE9vEzEQxS0EoqHwFdCqB24bZsb2OuYWRUuLVAnUwtlyHK_islkHe7el3x7nj1SJuYz0_Hvjp8fYFcIcscHPgPO79n4Oh-GNknwuoSliq1-xGUoStZAKX7NZede14hwu2LucHwBQcNJv2QUSbwTXYsZWSxc2oQvOjiEO1Y_kH_0w5qodNnHc-j7Yvlr5vq-W-7gfYw65Wj9Xy79FcGN4PLreszed7bP_cN6X7NfX9ufqpr79fv1ttbytndRK1tZCB0769aaza44LR1xLS41FsqoksiCU9Byd9-RIKbFAYSXoTndcik7wS_bpdHef4p_J59HsQnYlnB18nLJRhEIsRFPAq__AhziloWQzhCSISB6gLyfIpZhz8p3Zp7Cz6dkgmEPPBtCUns1Lz-bYs2l1MX88_zCtd37zYj0XWwBxAp5iP_qUf_fTk09m620_bo8nOSDVBEAIIKAuCkr-D59Yh2E</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>212422256</pqid></control><display><type>article</type><title>Acidification Prevents Endothelial Cell Apoptosis by Axl Activation</title><source>Journals@Ovid Ovid Autoload</source><source>MEDLINE</source><source>American Heart Association Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>D’Arcangelo, Daniela ; Gaetano, Carlo ; Capogrossi, Maurizio C</creator><creatorcontrib>D’Arcangelo, Daniela ; Gaetano, Carlo ; Capogrossi, Maurizio C</creatorcontrib><description><![CDATA[ABSTRACT—Prior studies have shown that acidification due to hypercarbia protects endothelial cells from serum deprivation–induced apoptosis. However, the mechanism(s) responsible for the antiapoptotic effect of acidification is still unclear. cDNA array screening was performed on human umbilical vein endothelial cells cultured in a bicarbonate medium equilibrated either with 5% CO2 (pH 7.4) or with 20% CO2 (pH 7.0). Tyrosine kinase receptor Axl expression was 3.3-fold higher after 6 hours at pH 7.0 compared with pH 7.4; this modulation was confirmed by reverse transcriptase–polymerase chain reaction (3.0±0.9-fold, P <0.03; n=3), Northern blot (3.6±0.1-fold, P <0.0003; n=3), and Western blot (10±1.8-fold, P <0.004; n=3). In a time-course study, both Northern and Western blot analyses showed that the most marked difference in Axl expression between pH 7.4 and pH 7.0 occurred after 24 to 48 hours. Furthermore, Axl phosphorylation was enhanced at pH 7.0. Axl ligand, the survival factor growth arrest–specific gene 6 product (Gas6), was released into the conditioned medium, and by Western blot analysis, similar amounts of protein were found at pH 7.0 and 7.4. Full-length Axl cDNA overexpression reduced serum deprivation–induced apoptosis by 64.4±11.9% in human umbilical vein endothelial cells cultured at pH 7.4 compared with mock-transfected cells (P <0.0004). Furthermore, overexpression of either soluble Axl or antisense Gas6 mRNA partially reverted the protective effect of acidification, increasing ≈2.5-fold the number of apoptotic cells at pH 7.0 (control 19.3±2.7%, soluble Axl 48.9±9.7%, P <0.001; antisense Gas6 49.3±14.3%, P <0.03). In conclusion, Gas6/Axl signaling may play an important role in endothelial cell survival during acidification. The full text of this article is available at http://www.circresaha.org.]]></description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.RES.0000036753.50601.E9</identifier><identifier>PMID: 12364394</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>Apoptosis ; Axl Receptor Tyrosine Kinase ; Cells, Cultured ; Culture Media, Conditioned - pharmacology ; Endothelium, Vascular - cytology ; Endothelium, Vascular - enzymology ; Enzyme Activation ; Humans ; Hydrogen-Ion Concentration ; Intercellular Signaling Peptides and Proteins ; Kinetics ; Oncogene Proteins - genetics ; Oncogene Proteins - metabolism ; Oncogene Proteins - physiology ; Proteins - genetics ; Proteins - physiology ; Proto-Oncogene Proteins ; Receptor Protein-Tyrosine Kinases - genetics ; Receptor Protein-Tyrosine Kinases - metabolism ; Receptor Protein-Tyrosine Kinases - physiology ; RNA, Messenger - biosynthesis ; Transfection</subject><ispartof>Circulation research, 2002-10, Vol.91 (7), p.e4-e12</ispartof><rights>2002 American Heart Association, Inc.</rights><rights>Copyright National Library of Medicine - MEDLINE Abstracts Oct 4 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5975-aa0f0c5ebdfab318c2395a26a12a7123a0475e31cee2c2774814a509f9f354f43</citedby><cites>FETCH-LOGICAL-c5975-aa0f0c5ebdfab318c2395a26a12a7123a0475e31cee2c2774814a509f9f354f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12364394$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>D’Arcangelo, Daniela</creatorcontrib><creatorcontrib>Gaetano, Carlo</creatorcontrib><creatorcontrib>Capogrossi, Maurizio C</creatorcontrib><title>Acidification Prevents Endothelial Cell Apoptosis by Axl Activation</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description><![CDATA[ABSTRACT—Prior studies have shown that acidification due to hypercarbia protects endothelial cells from serum deprivation–induced apoptosis. However, the mechanism(s) responsible for the antiapoptotic effect of acidification is still unclear. cDNA array screening was performed on human umbilical vein endothelial cells cultured in a bicarbonate medium equilibrated either with 5% CO2 (pH 7.4) or with 20% CO2 (pH 7.0). Tyrosine kinase receptor Axl expression was 3.3-fold higher after 6 hours at pH 7.0 compared with pH 7.4; this modulation was confirmed by reverse transcriptase–polymerase chain reaction (3.0±0.9-fold, P <0.03; n=3), Northern blot (3.6±0.1-fold, P <0.0003; n=3), and Western blot (10±1.8-fold, P <0.004; n=3). In a time-course study, both Northern and Western blot analyses showed that the most marked difference in Axl expression between pH 7.4 and pH 7.0 occurred after 24 to 48 hours. Furthermore, Axl phosphorylation was enhanced at pH 7.0. Axl ligand, the survival factor growth arrest–specific gene 6 product (Gas6), was released into the conditioned medium, and by Western blot analysis, similar amounts of protein were found at pH 7.0 and 7.4. Full-length Axl cDNA overexpression reduced serum deprivation–induced apoptosis by 64.4±11.9% in human umbilical vein endothelial cells cultured at pH 7.4 compared with mock-transfected cells (P <0.0004). Furthermore, overexpression of either soluble Axl or antisense Gas6 mRNA partially reverted the protective effect of acidification, increasing ≈2.5-fold the number of apoptotic cells at pH 7.0 (control 19.3±2.7%, soluble Axl 48.9±9.7%, P <0.001; antisense Gas6 49.3±14.3%, P <0.03). In conclusion, Gas6/Axl signaling may play an important role in endothelial cell survival during acidification. The full text of this article is available at http://www.circresaha.org.]]></description><subject>Apoptosis</subject><subject>Axl Receptor Tyrosine Kinase</subject><subject>Cells, Cultured</subject><subject>Culture Media, Conditioned - pharmacology</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - enzymology</subject><subject>Enzyme Activation</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Kinetics</subject><subject>Oncogene Proteins - genetics</subject><subject>Oncogene Proteins - metabolism</subject><subject>Oncogene Proteins - physiology</subject><subject>Proteins - genetics</subject><subject>Proteins - physiology</subject><subject>Proto-Oncogene Proteins</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Receptor Protein-Tyrosine Kinases - physiology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Transfection</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE9vEzEQxS0EoqHwFdCqB24bZsb2OuYWRUuLVAnUwtlyHK_islkHe7el3x7nj1SJuYz0_Hvjp8fYFcIcscHPgPO79n4Oh-GNknwuoSliq1-xGUoStZAKX7NZede14hwu2LucHwBQcNJv2QUSbwTXYsZWSxc2oQvOjiEO1Y_kH_0w5qodNnHc-j7Yvlr5vq-W-7gfYw65Wj9Xy79FcGN4PLreszed7bP_cN6X7NfX9ufqpr79fv1ttbytndRK1tZCB0769aaza44LR1xLS41FsqoksiCU9Byd9-RIKbFAYSXoTndcik7wS_bpdHef4p_J59HsQnYlnB18nLJRhEIsRFPAq__AhziloWQzhCSISB6gLyfIpZhz8p3Zp7Cz6dkgmEPPBtCUns1Lz-bYs2l1MX88_zCtd37zYj0XWwBxAp5iP_qUf_fTk09m620_bo8nOSDVBEAIIKAuCkr-D59Yh2E</recordid><startdate>20021004</startdate><enddate>20021004</enddate><creator>D’Arcangelo, Daniela</creator><creator>Gaetano, Carlo</creator><creator>Capogrossi, Maurizio C</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20021004</creationdate><title>Acidification Prevents Endothelial Cell Apoptosis by Axl Activation</title><author>D’Arcangelo, Daniela ; Gaetano, Carlo ; Capogrossi, Maurizio C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5975-aa0f0c5ebdfab318c2395a26a12a7123a0475e31cee2c2774814a509f9f354f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Apoptosis</topic><topic>Axl Receptor Tyrosine Kinase</topic><topic>Cells, Cultured</topic><topic>Culture Media, Conditioned - pharmacology</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - enzymology</topic><topic>Enzyme Activation</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Kinetics</topic><topic>Oncogene Proteins - genetics</topic><topic>Oncogene Proteins - metabolism</topic><topic>Oncogene Proteins - physiology</topic><topic>Proteins - genetics</topic><topic>Proteins - physiology</topic><topic>Proto-Oncogene Proteins</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Receptor Protein-Tyrosine Kinases - physiology</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>D’Arcangelo, Daniela</creatorcontrib><creatorcontrib>Gaetano, Carlo</creatorcontrib><creatorcontrib>Capogrossi, Maurizio C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>D’Arcangelo, Daniela</au><au>Gaetano, Carlo</au><au>Capogrossi, Maurizio C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acidification Prevents Endothelial Cell Apoptosis by Axl Activation</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2002-10-04</date><risdate>2002</risdate><volume>91</volume><issue>7</issue><spage>e4</spage><epage>e12</epage><pages>e4-e12</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract><![CDATA[ABSTRACT—Prior studies have shown that acidification due to hypercarbia protects endothelial cells from serum deprivation–induced apoptosis. However, the mechanism(s) responsible for the antiapoptotic effect of acidification is still unclear. cDNA array screening was performed on human umbilical vein endothelial cells cultured in a bicarbonate medium equilibrated either with 5% CO2 (pH 7.4) or with 20% CO2 (pH 7.0). Tyrosine kinase receptor Axl expression was 3.3-fold higher after 6 hours at pH 7.0 compared with pH 7.4; this modulation was confirmed by reverse transcriptase–polymerase chain reaction (3.0±0.9-fold, P <0.03; n=3), Northern blot (3.6±0.1-fold, P <0.0003; n=3), and Western blot (10±1.8-fold, P <0.004; n=3). In a time-course study, both Northern and Western blot analyses showed that the most marked difference in Axl expression between pH 7.4 and pH 7.0 occurred after 24 to 48 hours. Furthermore, Axl phosphorylation was enhanced at pH 7.0. Axl ligand, the survival factor growth arrest–specific gene 6 product (Gas6), was released into the conditioned medium, and by Western blot analysis, similar amounts of protein were found at pH 7.0 and 7.4. Full-length Axl cDNA overexpression reduced serum deprivation–induced apoptosis by 64.4±11.9% in human umbilical vein endothelial cells cultured at pH 7.4 compared with mock-transfected cells (P <0.0004). Furthermore, overexpression of either soluble Axl or antisense Gas6 mRNA partially reverted the protective effect of acidification, increasing ≈2.5-fold the number of apoptotic cells at pH 7.0 (control 19.3±2.7%, soluble Axl 48.9±9.7%, P <0.001; antisense Gas6 49.3±14.3%, P <0.03). In conclusion, Gas6/Axl signaling may play an important role in endothelial cell survival during acidification. The full text of this article is available at http://www.circresaha.org.]]></abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>12364394</pmid><doi>10.1161/01.RES.0000036753.50601.E9</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7330 |
| ispartof | Circulation research, 2002-10, Vol.91 (7), p.e4-e12 |
| issn | 0009-7330 1524-4571 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72144846 |
| source | Journals@Ovid Ovid Autoload; MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Apoptosis Axl Receptor Tyrosine Kinase Cells, Cultured Culture Media, Conditioned - pharmacology Endothelium, Vascular - cytology Endothelium, Vascular - enzymology Enzyme Activation Humans Hydrogen-Ion Concentration Intercellular Signaling Peptides and Proteins Kinetics Oncogene Proteins - genetics Oncogene Proteins - metabolism Oncogene Proteins - physiology Proteins - genetics Proteins - physiology Proto-Oncogene Proteins Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Receptor Protein-Tyrosine Kinases - physiology RNA, Messenger - biosynthesis Transfection |
| title | Acidification Prevents Endothelial Cell Apoptosis by Axl Activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T17%3A59%3A48IST&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=Acidification%20Prevents%20Endothelial%20Cell%20Apoptosis%20by%20Axl%20Activation&rft.jtitle=Circulation%20research&rft.au=D%E2%80%99Arcangelo,%20Daniela&rft.date=2002-10-04&rft.volume=91&rft.issue=7&rft.spage=e4&rft.epage=e12&rft.pages=e4-e12&rft.issn=0009-7330&rft.eissn=1524-4571&rft.coden=CIRUAL&rft_id=info:doi/10.1161/01.RES.0000036753.50601.E9&rft_dat=%3Cproquest_cross%3E72144846%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=212422256&rft_id=info:pmid/12364394&rfr_iscdi=true |