Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha

Pulmonary and Critical Care Medicine Section, Providence Veterans Affairs Medical Center, Brown University School of Medicine, Providence, Rhode Island 02908 Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs cause...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:American journal of physiology. Lung cellular and molecular physiology 2000-10, Vol.279 (4), p.733-L742
Hauptverfasser: Harrington, Elizabeth O, Smeglin, Anthony, Parks, Nancy, Newton, Julie, Rounds, Sharon
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page L742
container_issue 4
container_start_page 733
container_title American journal of physiology. Lung cellular and molecular physiology
container_volume 279
creator Harrington, Elizabeth O
Smeglin, Anthony
Parks, Nancy
Newton, Julie
Rounds, Sharon
description Pulmonary and Critical Care Medicine Section, Providence Veterans Affairs Medical Center, Brown University School of Medicine, Providence, Rhode Island 02908 Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S -adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH 2 -terminal kinase-1, or p38 activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38 activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38 activity. vascular endothelium; signal transduction; nucleotides; homocysteine
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_11000134</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72287604</sourcerecordid><originalsourceid>FETCH-LOGICAL-h1424-3a725a841d359bf7ad0e4830e8b8f1c86e607bb75d1fdb86b20a762cedb848f53</originalsourceid><addsrcrecordid>eNp1kEtLxTAQhYsovv-CZOWukFebXHcivuCCG12HpJneRnKb2KRq_72B68WVm5kzzHcOwxxUp6ShtCYN5odFY45r3OLmpDpL6R1j3GDcHlcnhBRNGD-twq2FMSQ3AnKjnTtICEYb8gDeaY90DDGXdUJmQbrL7lNnN25QnEIGN6K8TDtzHEKKg846wQ3SKIaUnPGAplBK6FFkUvsCXFRHvfYJLn_7efX2cP9691SvXx6f727X9UA45TXTgjZacmJZszK90BYDlwyDNLInnWyhxcIY0VjSWyNbQ7EWLe2gDFz2DTuvrne55dKPGVJWW5c68F6PEOakBKVStJgX8OoXnM0WrIqT2-ppUfsXFaDeAYPbDF9uAhWHJbngw2ZR-j36edwoKlaKq7VgrPCr__mH2ftX-M57459PRduzH4YkirQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72287604</pqid></control><display><type>article</type><title>Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha</title><source>MEDLINE</source><source>American Physiological Society Paid</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Harrington, Elizabeth O ; Smeglin, Anthony ; Parks, Nancy ; Newton, Julie ; Rounds, Sharon</creator><creatorcontrib>Harrington, Elizabeth O ; Smeglin, Anthony ; Parks, Nancy ; Newton, Julie ; Rounds, Sharon</creatorcontrib><description>Pulmonary and Critical Care Medicine Section, Providence Veterans Affairs Medical Center, Brown University School of Medicine, Providence, Rhode Island 02908 Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S -adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH 2 -terminal kinase-1, or p38 activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38 activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38 activity. vascular endothelium; signal transduction; nucleotides; homocysteine</description><identifier>ISSN: 1040-0605</identifier><identifier>EISSN: 1522-1504</identifier><identifier>PMID: 11000134</identifier><language>eng</language><publisher>United States</publisher><subject>Adenosine - analogs &amp; derivatives ; Adenosine - pharmacology ; Animals ; Apoptosis - drug effects ; Apoptosis - physiology ; Cattle ; Cell Line ; Cell Membrane - enzymology ; Cytosol - enzymology ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiology ; Enzyme Inhibitors - pharmacology ; Genistein - pharmacology ; JNK Mitogen-Activated Protein Kinases ; Kinetics ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 11 ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases - metabolism ; p38 Mitogen-Activated Protein Kinases ; Protein Tyrosine Phosphatases - metabolism ; Pulmonary Artery</subject><ispartof>American journal of physiology. Lung cellular and molecular physiology, 2000-10, Vol.279 (4), p.733-L742</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11000134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harrington, Elizabeth O</creatorcontrib><creatorcontrib>Smeglin, Anthony</creatorcontrib><creatorcontrib>Parks, Nancy</creatorcontrib><creatorcontrib>Newton, Julie</creatorcontrib><creatorcontrib>Rounds, Sharon</creatorcontrib><title>Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha</title><title>American journal of physiology. Lung cellular and molecular physiology</title><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><description>Pulmonary and Critical Care Medicine Section, Providence Veterans Affairs Medical Center, Brown University School of Medicine, Providence, Rhode Island 02908 Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S -adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH 2 -terminal kinase-1, or p38 activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38 activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38 activity. vascular endothelium; signal transduction; nucleotides; homocysteine</description><subject>Adenosine - analogs &amp; derivatives</subject><subject>Adenosine - pharmacology</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Cattle</subject><subject>Cell Line</subject><subject>Cell Membrane - enzymology</subject><subject>Cytosol - enzymology</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Genistein - pharmacology</subject><subject>JNK Mitogen-Activated Protein Kinases</subject><subject>Kinetics</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 11</subject><subject>Mitogen-Activated Protein Kinase 3</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>p38 Mitogen-Activated Protein Kinases</subject><subject>Protein Tyrosine Phosphatases - metabolism</subject><subject>Pulmonary Artery</subject><issn>1040-0605</issn><issn>1522-1504</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtLxTAQhYsovv-CZOWukFebXHcivuCCG12HpJneRnKb2KRq_72B68WVm5kzzHcOwxxUp6ShtCYN5odFY45r3OLmpDpL6R1j3GDcHlcnhBRNGD-twq2FMSQ3AnKjnTtICEYb8gDeaY90DDGXdUJmQbrL7lNnN25QnEIGN6K8TDtzHEKKg846wQ3SKIaUnPGAplBK6FFkUvsCXFRHvfYJLn_7efX2cP9691SvXx6f727X9UA45TXTgjZacmJZszK90BYDlwyDNLInnWyhxcIY0VjSWyNbQ7EWLe2gDFz2DTuvrne55dKPGVJWW5c68F6PEOakBKVStJgX8OoXnM0WrIqT2-ppUfsXFaDeAYPbDF9uAhWHJbngw2ZR-j36edwoKlaKq7VgrPCr__mH2ftX-M57459PRduzH4YkirQ</recordid><startdate>20001001</startdate><enddate>20001001</enddate><creator>Harrington, Elizabeth O</creator><creator>Smeglin, Anthony</creator><creator>Parks, Nancy</creator><creator>Newton, Julie</creator><creator>Rounds, Sharon</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20001001</creationdate><title>Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha</title><author>Harrington, Elizabeth O ; Smeglin, Anthony ; Parks, Nancy ; Newton, Julie ; Rounds, Sharon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h1424-3a725a841d359bf7ad0e4830e8b8f1c86e607bb75d1fdb86b20a762cedb848f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adenosine - analogs &amp; derivatives</topic><topic>Adenosine - pharmacology</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Cattle</topic><topic>Cell Line</topic><topic>Cell Membrane - enzymology</topic><topic>Cytosol - enzymology</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Genistein - pharmacology</topic><topic>JNK Mitogen-Activated Protein Kinases</topic><topic>Kinetics</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 11</topic><topic>Mitogen-Activated Protein Kinase 3</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>p38 Mitogen-Activated Protein Kinases</topic><topic>Protein Tyrosine Phosphatases - metabolism</topic><topic>Pulmonary Artery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harrington, Elizabeth O</creatorcontrib><creatorcontrib>Smeglin, Anthony</creatorcontrib><creatorcontrib>Parks, Nancy</creatorcontrib><creatorcontrib>Newton, Julie</creatorcontrib><creatorcontrib>Rounds, Sharon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harrington, Elizabeth O</au><au>Smeglin, Anthony</au><au>Parks, Nancy</au><au>Newton, Julie</au><au>Rounds, Sharon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha</atitle><jtitle>American journal of physiology. Lung cellular and molecular physiology</jtitle><addtitle>Am J Physiol Lung Cell Mol Physiol</addtitle><date>2000-10-01</date><risdate>2000</risdate><volume>279</volume><issue>4</issue><spage>733</spage><epage>L742</epage><pages>733-L742</pages><issn>1040-0605</issn><eissn>1522-1504</eissn><abstract>Pulmonary and Critical Care Medicine Section, Providence Veterans Affairs Medical Center, Brown University School of Medicine, Providence, Rhode Island 02908 Endothelial cell (EC) apoptosis is important in vascular injury, repair, and angiogenesis. Homocysteine and/or adenosine exposure of ECs causes apoptosis. Elevated homocysteine or adenosine occurs in disease states such as homocysteinuria and tissue necrosis, respectively. We examined the intracellular signaling mechanisms involved in this pathway of EC apoptosis. Inhibition of protein tyrosine phosphatase (PTPase) attenuated homocysteine- and/or adenosine-induced apoptosis and completely blocked apoptosis induced by the inhibition of S -adenosylhomocysteine hydrolase with MDL-28842. Consistent with this finding, the tyrosine kinase inhibitor genistein enhanced apoptosis in adenosine-treated ECs. Adenosine significantly elevated the PTPase activity in the ECs. Mitogen-activated protein kinase activities were examined to identify possible downstream targets for the upregulated PTPase(s). Extracellular signal-regulated kinase (ERK) 1 activity was slightly elevated in adenosine-treated ECs, whereas ERK2, c-Jun NH 2 -terminal kinase-1, or p38 activities differed little. The mitogen-activated protein kinase-1 inhibitor PD-98059 enhanced DNA fragmentation, suggesting that increased ERK1 activity is a result but not a cause of apoptosis in adenosine-treated ECs. Adenosine-treated ECs had diminished p38 activity compared with control cells; this effect was blunted on PTPase inhibition. These results indicate that PTPase(s) plays an integral role in the induction of EC apoptosis upon exposure to homocysteine and/or adenosine, possibly by the attenuation of p38 activity. vascular endothelium; signal transduction; nucleotides; homocysteine</abstract><cop>United States</cop><pmid>11000134</pmid></addata></record>
fulltext fulltext
identifier ISSN: 1040-0605
ispartof American journal of physiology. Lung cellular and molecular physiology, 2000-10, Vol.279 (4), p.733-L742
issn 1040-0605
1522-1504
language eng
recordid cdi_pubmed_primary_11000134
source MEDLINE; American Physiological Society Paid; EZB-FREE-00999 freely available EZB journals
subjects Adenosine - analogs & derivatives
Adenosine - pharmacology
Animals
Apoptosis - drug effects
Apoptosis - physiology
Cattle
Cell Line
Cell Membrane - enzymology
Cytosol - enzymology
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Enzyme Inhibitors - pharmacology
Genistein - pharmacology
JNK Mitogen-Activated Protein Kinases
Kinetics
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 11
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - metabolism
p38 Mitogen-Activated Protein Kinases
Protein Tyrosine Phosphatases - metabolism
Pulmonary Artery
title Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38alpha
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T02%3A59%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adenosine%20induces%20endothelial%20apoptosis%20by%20activating%20protein%20tyrosine%20phosphatase:%20a%20possible%20role%20of%20p38alpha&rft.jtitle=American%20journal%20of%20physiology.%20Lung%20cellular%20and%20molecular%20physiology&rft.au=Harrington,%20Elizabeth%20O&rft.date=2000-10-01&rft.volume=279&rft.issue=4&rft.spage=733&rft.epage=L742&rft.pages=733-L742&rft.issn=1040-0605&rft.eissn=1522-1504&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E72287604%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=72287604&rft_id=info:pmid/11000134&rfr_iscdi=true