Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo
ABSTRACT During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves acti...
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| Veröffentlicht in: | The FASEB journal 2003-07, Vol.17 (10), p.1355-1357 |
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| creator | Schulz, Rainer Gres, Petra Skyschally, Andreas Duschin, Alexej Belosjorow, Sergej Konietzka, Ina Heusch, Gerd |
| description | ABSTRACT
During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now studied in anesthetized pigs whether IP impacts on Cx43 phosphorylation by measuring the density of non‐phosphorylated and total Cx43 (confocal laser) during normoperfusion and 90‐min ischemia in non‐preconditioned and preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 and the activity of p38MAPK were assessed. IP by 10 min ischemia and 15 min reperfusion reduced IS. Non‐phosphorylated Cx43 remained unchanged during ischemia in preconditioned hearts, while it increased from 35±3 to 75±8 AU (P |
| doi_str_mv | 10.1096/fj.02-0975fje |
| format | Article |
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During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now studied in anesthetized pigs whether IP impacts on Cx43 phosphorylation by measuring the density of non‐phosphorylated and total Cx43 (confocal laser) during normoperfusion and 90‐min ischemia in non‐preconditioned and preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 and the activity of p38MAPK were assessed. IP by 10 min ischemia and 15 min reperfusion reduced IS. Non‐phosphorylated Cx43 remained unchanged during ischemia in preconditioned hearts, while it increased from 35±3 to 75±8 AU (P<0.05) in non‐preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 during ischemia increased only in preconditioned hearts. While the ischemia‐induced increase in p38MAPKα activity was comparable in preconditioned and non‐preconditioned hearts, p38MAPKβ activity was increased only in preconditioned hearts. Blockade of p38MAPK by SB203580 attenuated the IS‐reduction and the increased p38MAPK‐Cx43 co‐localization by IP. We conclude that IP increases co‐localization of protein kinases with Cx43 and preserves phosphorylation of Cx43 during ischemia.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.02-0975fje</identifier><identifier>PMID: 12759340</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Connexin 43 - analysis ; Connexin 43 - metabolism ; Enzyme Inhibitors - pharmacology ; Imidazoles - pharmacology ; Ischemic Preconditioning, Myocardial ; Kinetics ; Mitogen-Activated Protein Kinase 11 ; Mitogen-Activated Protein Kinase 14 ; Mitogen-Activated Protein Kinases - analysis ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinases - metabolism ; Models, Biological ; Myocardial Infarction - pathology ; Myocardial Ischemia - enzymology ; Myocardial Ischemia - metabolism ; Myocardium - chemistry ; Myocardium - enzymology ; Phosphorylation ; preconditioning ; Protein Kinase C - analysis ; Protein Kinase C-alpha ; Protein Kinase C-epsilon ; protein kinases ; Pyridines - pharmacology ; reperfusion ; Swine</subject><ispartof>The FASEB journal, 2003-07, Vol.17 (10), p.1355-1357</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.02-0975fje$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.02-0975fje$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12759340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schulz, Rainer</creatorcontrib><creatorcontrib>Gres, Petra</creatorcontrib><creatorcontrib>Skyschally, Andreas</creatorcontrib><creatorcontrib>Duschin, Alexej</creatorcontrib><creatorcontrib>Belosjorow, Sergej</creatorcontrib><creatorcontrib>Konietzka, Ina</creatorcontrib><creatorcontrib>Heusch, Gerd</creatorcontrib><title>Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now studied in anesthetized pigs whether IP impacts on Cx43 phosphorylation by measuring the density of non‐phosphorylated and total Cx43 (confocal laser) during normoperfusion and 90‐min ischemia in non‐preconditioned and preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 and the activity of p38MAPK were assessed. IP by 10 min ischemia and 15 min reperfusion reduced IS. Non‐phosphorylated Cx43 remained unchanged during ischemia in preconditioned hearts, while it increased from 35±3 to 75±8 AU (P<0.05) in non‐preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 during ischemia increased only in preconditioned hearts. While the ischemia‐induced increase in p38MAPKα activity was comparable in preconditioned and non‐preconditioned hearts, p38MAPKβ activity was increased only in preconditioned hearts. Blockade of p38MAPK by SB203580 attenuated the IS‐reduction and the increased p38MAPK‐Cx43 co‐localization by IP. We conclude that IP increases co‐localization of protein kinases with Cx43 and preserves phosphorylation of Cx43 during ischemia.</description><subject>Animals</subject><subject>Connexin 43 - analysis</subject><subject>Connexin 43 - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Imidazoles - pharmacology</subject><subject>Ischemic Preconditioning, Myocardial</subject><subject>Kinetics</subject><subject>Mitogen-Activated Protein Kinase 11</subject><subject>Mitogen-Activated Protein Kinase 14</subject><subject>Mitogen-Activated Protein Kinases - analysis</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Models, Biological</subject><subject>Myocardial Infarction - pathology</subject><subject>Myocardial Ischemia - enzymology</subject><subject>Myocardial Ischemia - metabolism</subject><subject>Myocardium - chemistry</subject><subject>Myocardium - enzymology</subject><subject>Phosphorylation</subject><subject>preconditioning</subject><subject>Protein Kinase C - analysis</subject><subject>Protein Kinase C-alpha</subject><subject>Protein Kinase C-epsilon</subject><subject>protein kinases</subject><subject>Pyridines - pharmacology</subject><subject>reperfusion</subject><subject>Swine</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEFPg0AQRjdGY2v16NVw8kYddlgWvGlTtE0TD-p5w8LQbkMBWaj23wtpjYfJ5Jt5mUweY7ceTD2Igod8OwXuQiRFvqUzNvYEghuEAZyzMYQRd4MAwxG7snYLAB54wSUbeVyKCH0Ys3Jh0w3tTOrUDaVVmZnWVKUp10O21OzJOv24pB9TOj469aayfTWHIhlAJ-uaAbadbRNTUuaY473E6fnarJ0NJU1rh7Q3--qaXeRJYenm1CfsM55_zF7d1dvLYva0cmsvgrkrde5HqDONIYUCAy0zyBKtEQRHFBoJNEjhY8b9QPjkoc9DiVxwSnPJNU7Y_fFu3VRfHdlW7frHqCiSkqrOKol-L0pCD96dwE7vKFN1Y3ZJc1B_hnrg8Qh8m4IO_3tQg36VbxVwddKv4vdnHi-BDzlezvEXRxB7yQ</recordid><startdate>200307</startdate><enddate>200307</enddate><creator>Schulz, Rainer</creator><creator>Gres, Petra</creator><creator>Skyschally, Andreas</creator><creator>Duschin, Alexej</creator><creator>Belosjorow, Sergej</creator><creator>Konietzka, Ina</creator><creator>Heusch, Gerd</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>200307</creationdate><title>Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo</title><author>Schulz, Rainer ; Gres, Petra ; Skyschally, Andreas ; Duschin, Alexej ; Belosjorow, Sergej ; Konietzka, Ina ; Heusch, Gerd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p190E-7bf493bdb38e8536b7d0dabb3052335b3e0b07543d24654e1342873252ecf72b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Connexin 43 - analysis</topic><topic>Connexin 43 - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Imidazoles - pharmacology</topic><topic>Ischemic Preconditioning, Myocardial</topic><topic>Kinetics</topic><topic>Mitogen-Activated Protein Kinase 11</topic><topic>Mitogen-Activated Protein Kinase 14</topic><topic>Mitogen-Activated Protein Kinases - analysis</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Models, Biological</topic><topic>Myocardial Infarction - pathology</topic><topic>Myocardial Ischemia - enzymology</topic><topic>Myocardial Ischemia - metabolism</topic><topic>Myocardium - chemistry</topic><topic>Myocardium - enzymology</topic><topic>Phosphorylation</topic><topic>preconditioning</topic><topic>Protein Kinase C - analysis</topic><topic>Protein Kinase C-alpha</topic><topic>Protein Kinase C-epsilon</topic><topic>protein kinases</topic><topic>Pyridines - pharmacology</topic><topic>reperfusion</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schulz, Rainer</creatorcontrib><creatorcontrib>Gres, Petra</creatorcontrib><creatorcontrib>Skyschally, Andreas</creatorcontrib><creatorcontrib>Duschin, Alexej</creatorcontrib><creatorcontrib>Belosjorow, Sergej</creatorcontrib><creatorcontrib>Konietzka, Ina</creatorcontrib><creatorcontrib>Heusch, Gerd</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>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schulz, Rainer</au><au>Gres, Petra</au><au>Skyschally, Andreas</au><au>Duschin, Alexej</au><au>Belosjorow, Sergej</au><au>Konietzka, Ina</au><au>Heusch, Gerd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2003-07</date><risdate>2003</risdate><volume>17</volume><issue>10</issue><spage>1355</spage><epage>1357</epage><pages>1355-1357</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now studied in anesthetized pigs whether IP impacts on Cx43 phosphorylation by measuring the density of non‐phosphorylated and total Cx43 (confocal laser) during normoperfusion and 90‐min ischemia in non‐preconditioned and preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 and the activity of p38MAPK were assessed. IP by 10 min ischemia and 15 min reperfusion reduced IS. Non‐phosphorylated Cx43 remained unchanged during ischemia in preconditioned hearts, while it increased from 35±3 to 75±8 AU (P<0.05) in non‐preconditioned hearts. Co‐localization of PKCα, p38MAPKα, and p38MAPKβ with Cx43 during ischemia increased only in preconditioned hearts. While the ischemia‐induced increase in p38MAPKα activity was comparable in preconditioned and non‐preconditioned hearts, p38MAPKβ activity was increased only in preconditioned hearts. Blockade of p38MAPK by SB203580 attenuated the IS‐reduction and the increased p38MAPK‐Cx43 co‐localization by IP. We conclude that IP increases co‐localization of protein kinases with Cx43 and preserves phosphorylation of Cx43 during ischemia.</abstract><cop>United States</cop><pmid>12759340</pmid><doi>10.1096/fj.02-0975fje</doi><tpages>22</tpages></addata></record> |
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| subjects | Animals Connexin 43 - analysis Connexin 43 - metabolism Enzyme Inhibitors - pharmacology Imidazoles - pharmacology Ischemic Preconditioning, Myocardial Kinetics Mitogen-Activated Protein Kinase 11 Mitogen-Activated Protein Kinase 14 Mitogen-Activated Protein Kinases - analysis Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - metabolism Models, Biological Myocardial Infarction - pathology Myocardial Ischemia - enzymology Myocardial Ischemia - metabolism Myocardium - chemistry Myocardium - enzymology Phosphorylation preconditioning Protein Kinase C - analysis Protein Kinase C-alpha Protein Kinase C-epsilon protein kinases Pyridines - pharmacology reperfusion Swine |
| title | Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo |
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