HYPO-OSMOTIC STRESS INHIBITS DOXORUBICIN-INDUCED APOPTOSIS VIA A PROTEIN KINASE A-DEPENDENT MECHANISM IN CARDIOMYOCYTES

SUMMARY 1. The clinical use of doxorubicin is limited by the development of severe cardiomyopathies linked, at least in part, to an abnormal increase in the rate of apoptotic cell death. Because cell shrinkage is considered to be a crucial step at the onset of apoptosis, the aim of the present study...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Clinical and experimental pharmacology & physiology 2004-07, Vol.31 (7), p.438-443
Hauptverfasser: D'Anglemont De Tassigny, Alexandra, Ghaleh, Bijan, Souktani, Rachid, Henry, Patrick, Berdeaux, Alain
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 443
container_issue 7
container_start_page 438
container_title Clinical and experimental pharmacology & physiology
container_volume 31
creator D'Anglemont De Tassigny, Alexandra
Ghaleh, Bijan
Souktani, Rachid
Henry, Patrick
Berdeaux, Alain
description SUMMARY 1. The clinical use of doxorubicin is limited by the development of severe cardiomyopathies linked, at least in part, to an abnormal increase in the rate of apoptotic cell death. Because cell shrinkage is considered to be a crucial step at the onset of apoptosis, the aim of the present study was to investigate whether a brief hypo‐osmotic stress, which leads to an increase in cell volume, could interfere with the induction of apoptosis by doxorubicin in adult cardiomyocytes. 2. Cell volume expansion results in intracellular accumulation of cAMP, so we secondarily tested whether the protective effect of hypo‐osmotic stress could be related to the cAMP pathway. Accordingly, apoptosis was induced by doxorubicin (1 µmol/L) in cardiomyocytes freshly isolated from New Zealand adult rabbit hearts. 3. Exposure to doxorubicin in an iso‐osmotic medium (290 mOsmol/kg H2O) induced a rapid decrease in cell volume, as well as increases in annexin V labelling and caspase‐3 activity, two biological markers of apoptosis. These effects of doxorubicin were abolished by 15 min pretreatment with hypo‐osmotic stress at 220 mOsmol/kgH2O (HS 220). 4. This cytoprotective effect of HS 220 was still observed when doxorubicin was added to the medium 60 min later, but it was abolished when the pretreatment by HS 220 was associated with the protein kinase A inhibitor KT 5720 (200 nmol/L). 5. Conversely, 15 min pretreatment with either the cAMP analogue 8‐bromo‐cAMP (0.5 mmol/L) or the adenylate cyclase activator forskolin (10 µmol/L) inhibited apoptosis induced by doxorubicin. 6. In conclusion, these results demonstrate that: (i) apoptosis induced by doxorubicin can be counteracted by a hypo‐osmotic stress in adult cardiomyocytes; and (ii) activation of the protein kinase A‐dependent pathway plays a major role in the mechanism leading to the cytoprotective effect induced by a hypo‐osmotic stress.
doi_str_mv 10.1111/j.1440-1681.2004.04025.x
format Article
fullrecord <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04439739v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66680044</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5035-94db7aa5b9d5ac6f2fe3c0f5e06ced572029a96acd15dc4837586e7486fd879f3</originalsourceid><addsrcrecordid>eNqNkUFvmzAYhq1p1Zpl-wuTT5N2gNkYGzjsQMEr7hKMAtmaXiwHjJaULB00a_rvCyPKrvPFlv287yf5AQBiZON-fd7a2HWRhZmPbQch10Yucqh9fAUm54fXYIIIohb2PXQJ3nbdFiFEESNvwCWmDmGM4Al4SlaZtGQ-l4WIYF4seJ5DkSbiShQ5jOWtXCyvRCRSS6TxMuIxDDOZFTIXOfwuQhjCbCELLlL4TaRhzmFoxTzjaczTAs55lISpyOd9I4zCRSzkfCWjVcHzd-Ci1k1n3p_2KVh-5UWUWDN5LaJwZpUUEWoFbrX2tKbroKK6ZLVTG1KimhrESlNRz0FOoAOmywrTqnR94lGfGc_1WV35XlCTKfg09v7UjXpoNzvdPqu93qgknKnhDrkuCTwS_ME9-3FkH9r974PpHtVu05WmafQvsz90ijHmo4GfAn8Ey3bfda2pz80YqUGQ2qrBgxo8qEGQ-itIHfvoh9OMw3pnqn_Bk5Ee-DICT5vGPP93sYp4Npz6vDXmN92jOZ7zur1XzOu_R_1Ir1WRBfT25u5G3ZEXxpyjiA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66680044</pqid></control><display><type>article</type><title>HYPO-OSMOTIC STRESS INHIBITS DOXORUBICIN-INDUCED APOPTOSIS VIA A PROTEIN KINASE A-DEPENDENT MECHANISM IN CARDIOMYOCYTES</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>D'Anglemont De Tassigny, Alexandra ; Ghaleh, Bijan ; Souktani, Rachid ; Henry, Patrick ; Berdeaux, Alain</creator><creatorcontrib>D'Anglemont De Tassigny, Alexandra ; Ghaleh, Bijan ; Souktani, Rachid ; Henry, Patrick ; Berdeaux, Alain</creatorcontrib><description>SUMMARY 1. The clinical use of doxorubicin is limited by the development of severe cardiomyopathies linked, at least in part, to an abnormal increase in the rate of apoptotic cell death. Because cell shrinkage is considered to be a crucial step at the onset of apoptosis, the aim of the present study was to investigate whether a brief hypo‐osmotic stress, which leads to an increase in cell volume, could interfere with the induction of apoptosis by doxorubicin in adult cardiomyocytes. 2. Cell volume expansion results in intracellular accumulation of cAMP, so we secondarily tested whether the protective effect of hypo‐osmotic stress could be related to the cAMP pathway. Accordingly, apoptosis was induced by doxorubicin (1 µmol/L) in cardiomyocytes freshly isolated from New Zealand adult rabbit hearts. 3. Exposure to doxorubicin in an iso‐osmotic medium (290 mOsmol/kg H2O) induced a rapid decrease in cell volume, as well as increases in annexin V labelling and caspase‐3 activity, two biological markers of apoptosis. These effects of doxorubicin were abolished by 15 min pretreatment with hypo‐osmotic stress at 220 mOsmol/kgH2O (HS 220). 4. This cytoprotective effect of HS 220 was still observed when doxorubicin was added to the medium 60 min later, but it was abolished when the pretreatment by HS 220 was associated with the protein kinase A inhibitor KT 5720 (200 nmol/L). 5. Conversely, 15 min pretreatment with either the cAMP analogue 8‐bromo‐cAMP (0.5 mmol/L) or the adenylate cyclase activator forskolin (10 µmol/L) inhibited apoptosis induced by doxorubicin. 6. In conclusion, these results demonstrate that: (i) apoptosis induced by doxorubicin can be counteracted by a hypo‐osmotic stress in adult cardiomyocytes; and (ii) activation of the protein kinase A‐dependent pathway plays a major role in the mechanism leading to the cytoprotective effect induced by a hypo‐osmotic stress.</description><identifier>ISSN: 0305-1870</identifier><identifier>EISSN: 1440-1681</identifier><identifier>DOI: 10.1111/j.1440-1681.2004.04025.x</identifier><identifier>PMID: 15236631</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Pty</publisher><subject>8-Bromo Cyclic Adenosine Monophosphate - pharmacology ; Animals ; Annexin A5 - metabolism ; Anti-Bacterial Agents - pharmacology ; apoptosis ; Apoptosis - drug effects ; Caspase 3 ; Caspases - metabolism ; Cell Separation ; Cell Size - drug effects ; cell volume ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - physiology ; doxorubicin ; Doxorubicin - pharmacology ; Enzyme Inhibitors - metabolism ; hypo-osmotic stress ; In Vitro Techniques ; Life Sciences ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - physiology ; Osmotic Pressure ; protein kinase A ; Rabbits</subject><ispartof>Clinical and experimental pharmacology &amp; physiology, 2004-07, Vol.31 (7), p.438-443</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5035-94db7aa5b9d5ac6f2fe3c0f5e06ced572029a96acd15dc4837586e7486fd879f3</citedby><cites>FETCH-LOGICAL-c5035-94db7aa5b9d5ac6f2fe3c0f5e06ced572029a96acd15dc4837586e7486fd879f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1440-1681.2004.04025.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1440-1681.2004.04025.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15236631$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04439739$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>D'Anglemont De Tassigny, Alexandra</creatorcontrib><creatorcontrib>Ghaleh, Bijan</creatorcontrib><creatorcontrib>Souktani, Rachid</creatorcontrib><creatorcontrib>Henry, Patrick</creatorcontrib><creatorcontrib>Berdeaux, Alain</creatorcontrib><title>HYPO-OSMOTIC STRESS INHIBITS DOXORUBICIN-INDUCED APOPTOSIS VIA A PROTEIN KINASE A-DEPENDENT MECHANISM IN CARDIOMYOCYTES</title><title>Clinical and experimental pharmacology &amp; physiology</title><addtitle>Clin Exp Pharmacol Physiol</addtitle><description>SUMMARY 1. The clinical use of doxorubicin is limited by the development of severe cardiomyopathies linked, at least in part, to an abnormal increase in the rate of apoptotic cell death. Because cell shrinkage is considered to be a crucial step at the onset of apoptosis, the aim of the present study was to investigate whether a brief hypo‐osmotic stress, which leads to an increase in cell volume, could interfere with the induction of apoptosis by doxorubicin in adult cardiomyocytes. 2. Cell volume expansion results in intracellular accumulation of cAMP, so we secondarily tested whether the protective effect of hypo‐osmotic stress could be related to the cAMP pathway. Accordingly, apoptosis was induced by doxorubicin (1 µmol/L) in cardiomyocytes freshly isolated from New Zealand adult rabbit hearts. 3. Exposure to doxorubicin in an iso‐osmotic medium (290 mOsmol/kg H2O) induced a rapid decrease in cell volume, as well as increases in annexin V labelling and caspase‐3 activity, two biological markers of apoptosis. These effects of doxorubicin were abolished by 15 min pretreatment with hypo‐osmotic stress at 220 mOsmol/kgH2O (HS 220). 4. This cytoprotective effect of HS 220 was still observed when doxorubicin was added to the medium 60 min later, but it was abolished when the pretreatment by HS 220 was associated with the protein kinase A inhibitor KT 5720 (200 nmol/L). 5. Conversely, 15 min pretreatment with either the cAMP analogue 8‐bromo‐cAMP (0.5 mmol/L) or the adenylate cyclase activator forskolin (10 µmol/L) inhibited apoptosis induced by doxorubicin. 6. In conclusion, these results demonstrate that: (i) apoptosis induced by doxorubicin can be counteracted by a hypo‐osmotic stress in adult cardiomyocytes; and (ii) activation of the protein kinase A‐dependent pathway plays a major role in the mechanism leading to the cytoprotective effect induced by a hypo‐osmotic stress.</description><subject>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</subject><subject>Animals</subject><subject>Annexin A5 - metabolism</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Cell Separation</subject><subject>Cell Size - drug effects</subject><subject>cell volume</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - physiology</subject><subject>doxorubicin</subject><subject>Doxorubicin - pharmacology</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>hypo-osmotic stress</subject><subject>In Vitro Techniques</subject><subject>Life Sciences</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - physiology</subject><subject>Osmotic Pressure</subject><subject>protein kinase A</subject><subject>Rabbits</subject><issn>0305-1870</issn><issn>1440-1681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUFvmzAYhq1p1Zpl-wuTT5N2gNkYGzjsQMEr7hKMAtmaXiwHjJaULB00a_rvCyPKrvPFlv287yf5AQBiZON-fd7a2HWRhZmPbQch10Yucqh9fAUm54fXYIIIohb2PXQJ3nbdFiFEESNvwCWmDmGM4Al4SlaZtGQ-l4WIYF4seJ5DkSbiShQ5jOWtXCyvRCRSS6TxMuIxDDOZFTIXOfwuQhjCbCELLlL4TaRhzmFoxTzjaczTAs55lISpyOd9I4zCRSzkfCWjVcHzd-Ci1k1n3p_2KVh-5UWUWDN5LaJwZpUUEWoFbrX2tKbroKK6ZLVTG1KimhrESlNRz0FOoAOmywrTqnR94lGfGc_1WV35XlCTKfg09v7UjXpoNzvdPqu93qgknKnhDrkuCTwS_ME9-3FkH9r974PpHtVu05WmafQvsz90ijHmo4GfAn8Ey3bfda2pz80YqUGQ2qrBgxo8qEGQ-itIHfvoh9OMw3pnqn_Bk5Ee-DICT5vGPP93sYp4Npz6vDXmN92jOZ7zur1XzOu_R_1Ir1WRBfT25u5G3ZEXxpyjiA</recordid><startdate>200407</startdate><enddate>200407</enddate><creator>D'Anglemont De Tassigny, Alexandra</creator><creator>Ghaleh, Bijan</creator><creator>Souktani, Rachid</creator><creator>Henry, Patrick</creator><creator>Berdeaux, Alain</creator><general>Blackwell Science Pty</general><general>Wiley</general><scope>BSCLL</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><scope>1XC</scope></search><sort><creationdate>200407</creationdate><title>HYPO-OSMOTIC STRESS INHIBITS DOXORUBICIN-INDUCED APOPTOSIS VIA A PROTEIN KINASE A-DEPENDENT MECHANISM IN CARDIOMYOCYTES</title><author>D'Anglemont De Tassigny, Alexandra ; Ghaleh, Bijan ; Souktani, Rachid ; Henry, Patrick ; Berdeaux, Alain</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5035-94db7aa5b9d5ac6f2fe3c0f5e06ced572029a96acd15dc4837586e7486fd879f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</topic><topic>Animals</topic><topic>Annexin A5 - metabolism</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Cell Separation</topic><topic>Cell Size - drug effects</topic><topic>cell volume</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - physiology</topic><topic>doxorubicin</topic><topic>Doxorubicin - pharmacology</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>hypo-osmotic stress</topic><topic>In Vitro Techniques</topic><topic>Life Sciences</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - physiology</topic><topic>Osmotic Pressure</topic><topic>protein kinase A</topic><topic>Rabbits</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>D'Anglemont De Tassigny, Alexandra</creatorcontrib><creatorcontrib>Ghaleh, Bijan</creatorcontrib><creatorcontrib>Souktani, Rachid</creatorcontrib><creatorcontrib>Henry, Patrick</creatorcontrib><creatorcontrib>Berdeaux, Alain</creatorcontrib><collection>Istex</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><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Clinical and experimental pharmacology &amp; physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>D'Anglemont De Tassigny, Alexandra</au><au>Ghaleh, Bijan</au><au>Souktani, Rachid</au><au>Henry, Patrick</au><au>Berdeaux, Alain</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HYPO-OSMOTIC STRESS INHIBITS DOXORUBICIN-INDUCED APOPTOSIS VIA A PROTEIN KINASE A-DEPENDENT MECHANISM IN CARDIOMYOCYTES</atitle><jtitle>Clinical and experimental pharmacology &amp; physiology</jtitle><addtitle>Clin Exp Pharmacol Physiol</addtitle><date>2004-07</date><risdate>2004</risdate><volume>31</volume><issue>7</issue><spage>438</spage><epage>443</epage><pages>438-443</pages><issn>0305-1870</issn><eissn>1440-1681</eissn><abstract>SUMMARY 1. The clinical use of doxorubicin is limited by the development of severe cardiomyopathies linked, at least in part, to an abnormal increase in the rate of apoptotic cell death. Because cell shrinkage is considered to be a crucial step at the onset of apoptosis, the aim of the present study was to investigate whether a brief hypo‐osmotic stress, which leads to an increase in cell volume, could interfere with the induction of apoptosis by doxorubicin in adult cardiomyocytes. 2. Cell volume expansion results in intracellular accumulation of cAMP, so we secondarily tested whether the protective effect of hypo‐osmotic stress could be related to the cAMP pathway. Accordingly, apoptosis was induced by doxorubicin (1 µmol/L) in cardiomyocytes freshly isolated from New Zealand adult rabbit hearts. 3. Exposure to doxorubicin in an iso‐osmotic medium (290 mOsmol/kg H2O) induced a rapid decrease in cell volume, as well as increases in annexin V labelling and caspase‐3 activity, two biological markers of apoptosis. These effects of doxorubicin were abolished by 15 min pretreatment with hypo‐osmotic stress at 220 mOsmol/kgH2O (HS 220). 4. This cytoprotective effect of HS 220 was still observed when doxorubicin was added to the medium 60 min later, but it was abolished when the pretreatment by HS 220 was associated with the protein kinase A inhibitor KT 5720 (200 nmol/L). 5. Conversely, 15 min pretreatment with either the cAMP analogue 8‐bromo‐cAMP (0.5 mmol/L) or the adenylate cyclase activator forskolin (10 µmol/L) inhibited apoptosis induced by doxorubicin. 6. In conclusion, these results demonstrate that: (i) apoptosis induced by doxorubicin can be counteracted by a hypo‐osmotic stress in adult cardiomyocytes; and (ii) activation of the protein kinase A‐dependent pathway plays a major role in the mechanism leading to the cytoprotective effect induced by a hypo‐osmotic stress.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Pty</pub><pmid>15236631</pmid><doi>10.1111/j.1440-1681.2004.04025.x</doi><tpages>6</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0305-1870
ispartof Clinical and experimental pharmacology & physiology, 2004-07, Vol.31 (7), p.438-443
issn 0305-1870
1440-1681
language eng
recordid cdi_hal_primary_oai_HAL_hal_04439739v1
source MEDLINE; Access via Wiley Online Library
subjects 8-Bromo Cyclic Adenosine Monophosphate - pharmacology
Animals
Annexin A5 - metabolism
Anti-Bacterial Agents - pharmacology
apoptosis
Apoptosis - drug effects
Caspase 3
Caspases - metabolism
Cell Separation
Cell Size - drug effects
cell volume
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - physiology
doxorubicin
Doxorubicin - pharmacology
Enzyme Inhibitors - metabolism
hypo-osmotic stress
In Vitro Techniques
Life Sciences
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - physiology
Osmotic Pressure
protein kinase A
Rabbits
title HYPO-OSMOTIC STRESS INHIBITS DOXORUBICIN-INDUCED APOPTOSIS VIA A PROTEIN KINASE A-DEPENDENT MECHANISM IN CARDIOMYOCYTES
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T22%3A41%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=HYPO-OSMOTIC%20STRESS%20INHIBITS%20DOXORUBICIN-INDUCED%20APOPTOSIS%20VIA%20A%20PROTEIN%20KINASE%20A-DEPENDENT%20MECHANISM%20IN%20CARDIOMYOCYTES&rft.jtitle=Clinical%20and%20experimental%20pharmacology%20&%20physiology&rft.au=D'Anglemont%20De%20Tassigny,%20Alexandra&rft.date=2004-07&rft.volume=31&rft.issue=7&rft.spage=438&rft.epage=443&rft.pages=438-443&rft.issn=0305-1870&rft.eissn=1440-1681&rft_id=info:doi/10.1111/j.1440-1681.2004.04025.x&rft_dat=%3Cproquest_hal_p%3E66680044%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66680044&rft_id=info:pmid/15236631&rfr_iscdi=true