Upregulation of TACE/ADAM17 after ischemic preconditioning is involved in brain tolerance
A short ischemic event (ischemic preconditioning [IPC]) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance [IT]). Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been...
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| Veröffentlicht in: | Journal of cerebral blood flow and metabolism 2002-11, Vol.22 (11), p.1297-1302 |
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| container_title | Journal of cerebral blood flow and metabolism |
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| creator | CARDENAS, Antonio MORO, Maria A LEZA, Juan C O'SHEA, Esther DAVALOS, Antoni CASTILLO, José LORENZO, Pedro LIZASOAIN, Ignacio |
| description | A short ischemic event (ischemic preconditioning [IPC]) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance [IT]). Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-alpha convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-alpha release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-alpha release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg. kg(-1). day(-1); SHAM, 1,050 +/- 180; IPC, 1,870 +/- 290; IPC + BB, 1,320 +/- 260 ng/mg; n = 4, < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti-TNF-alpha (10 microg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 +/- 20; IPC + pMCAO, 244 +/- 14; IPC + BB + pMCAO, 300 +/- 6; IPC + anti-TNF + pMCAO, 348 +/- 22 mm3; n = 6-10, < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-alpha shedding in IPC, and has a neuroprotective role in IT. |
| doi_str_mv | 10.1097/00004647-200211000-00002 |
| format | Article |
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Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-alpha convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-alpha release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-alpha release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg. kg(-1). day(-1); SHAM, 1,050 +/- 180; IPC, 1,870 +/- 290; IPC + BB, 1,320 +/- 260 ng/mg; n = 4, < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti-TNF-alpha (10 microg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 +/- 20; IPC + pMCAO, 244 +/- 14; IPC + BB + pMCAO, 300 +/- 6; IPC + anti-TNF + pMCAO, 348 +/- 22 mm3; n = 6-10, < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-alpha shedding in IPC, and has a neuroprotective role in IT.</description><identifier>ISSN: 0271-678X</identifier><identifier>EISSN: 1559-7016</identifier><identifier>DOI: 10.1097/00004647-200211000-00002</identifier><identifier>PMID: 12439286</identifier><identifier>CODEN: JCBMDN</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>ADAM Proteins ; ADAM17 Protein ; Animals ; Biological and medical sciences ; Brain - metabolism ; Brain - physiopathology ; Cerebral Infarction - metabolism ; Cerebral Infarction - pathology ; Infarction, Middle Cerebral Artery - metabolism ; Infarction, Middle Cerebral Artery - physiopathology ; Ischemic Preconditioning ; Male ; Medical sciences ; Metalloendopeptidases - antagonists & inhibitors ; Metalloendopeptidases - metabolism ; Neurology ; Rats ; Rats, Inbred F344 ; Tumor Necrosis Factor-alpha - metabolism ; Up-Regulation ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Journal of cerebral blood flow and metabolism, 2002-11, Vol.22 (11), p.1297-1302</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Nov 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3136-c238a7c8978f103869cf3c3801bde719f9f43809664069766f7ba1eb8597fb7d3</citedby><cites>FETCH-LOGICAL-c3136-c238a7c8978f103869cf3c3801bde719f9f43809664069766f7ba1eb8597fb7d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13998670$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12439286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CARDENAS, Antonio</creatorcontrib><creatorcontrib>MORO, Maria A</creatorcontrib><creatorcontrib>LEZA, Juan C</creatorcontrib><creatorcontrib>O'SHEA, Esther</creatorcontrib><creatorcontrib>DAVALOS, Antoni</creatorcontrib><creatorcontrib>CASTILLO, José</creatorcontrib><creatorcontrib>LORENZO, Pedro</creatorcontrib><creatorcontrib>LIZASOAIN, Ignacio</creatorcontrib><title>Upregulation of TACE/ADAM17 after ischemic preconditioning is involved in brain tolerance</title><title>Journal of cerebral blood flow and metabolism</title><addtitle>J Cereb Blood Flow Metab</addtitle><description>A short ischemic event (ischemic preconditioning [IPC]) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance [IT]). Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-alpha convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-alpha release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-alpha release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg. kg(-1). day(-1); SHAM, 1,050 +/- 180; IPC, 1,870 +/- 290; IPC + BB, 1,320 +/- 260 ng/mg; n = 4, < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti-TNF-alpha (10 microg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 +/- 20; IPC + pMCAO, 244 +/- 14; IPC + BB + pMCAO, 300 +/- 6; IPC + anti-TNF + pMCAO, 348 +/- 22 mm3; n = 6-10, < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-alpha shedding in IPC, and has a neuroprotective role in IT.</description><subject>ADAM Proteins</subject><subject>ADAM17 Protein</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>Brain - physiopathology</subject><subject>Cerebral Infarction - metabolism</subject><subject>Cerebral Infarction - pathology</subject><subject>Infarction, Middle Cerebral Artery - metabolism</subject><subject>Infarction, Middle Cerebral Artery - physiopathology</subject><subject>Ischemic Preconditioning</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metalloendopeptidases - antagonists & inhibitors</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Neurology</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Up-Regulation</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0271-678X</issn><issn>1559-7016</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kctOwzAQRS0EouXxCyhCAlYBj534sazKUypi00qwihzHLqnSuNhNJf4eBwpILJiFxzM-c2X7IpQAvgQs-RWOkbGMpwRjAhCrtG-RHTSEPJcpx8B20RATDinj4nmADkJYRELQPN9HAyAZlUSwIXqZrbyZd41a165NnE2mo_HN1eh69Ag8UXZtfFIH_WqWtU4iqV1b1T1at_N4kNTtxjUbU8VNUnoV17VrjFetNkdoz6ommONtPkSz25vp-D6dPN09jEeTVFOgLNWECsW1kFxYwFQwqS3VVGAoK8NBWmmzWEnGMswkZ8zyUoEpRS65LXlFD9HFl-7Ku7fOhHWxjDc2TaNa47pQCM4IkRTySJ7_S3LCBM0IieDpH3DhOt_GVxQEZE5zABoh8QVp70LwxhYrXy-Vfy8AF71LxbdLxY9Ln61e_2Sr35VLU_0Obm2JwNkWUEGrxvYfWodfjkopGMf0A8fkl0k</recordid><startdate>200211</startdate><enddate>200211</enddate><creator>CARDENAS, Antonio</creator><creator>MORO, Maria A</creator><creator>LEZA, Juan C</creator><creator>O'SHEA, Esther</creator><creator>DAVALOS, Antoni</creator><creator>CASTILLO, José</creator><creator>LORENZO, Pedro</creator><creator>LIZASOAIN, Ignacio</creator><general>Lippincott Williams & Wilkins</general><general>Sage Publications Ltd</general><scope>IQODW</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>200211</creationdate><title>Upregulation of TACE/ADAM17 after ischemic preconditioning is involved in brain tolerance</title><author>CARDENAS, Antonio ; 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Although tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-alpha convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-alpha release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-alpha release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg. kg(-1). day(-1); SHAM, 1,050 +/- 180; IPC, 1,870 +/- 290; IPC + BB, 1,320 +/- 260 ng/mg; n = 4, < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti-TNF-alpha (10 microg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 +/- 20; IPC + pMCAO, 244 +/- 14; IPC + BB + pMCAO, 300 +/- 6; IPC + anti-TNF + pMCAO, 348 +/- 22 mm3; n = 6-10, < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-alpha shedding in IPC, and has a neuroprotective role in IT.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12439286</pmid><doi>10.1097/00004647-200211000-00002</doi><tpages>6</tpages></addata></record> |
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| subjects | ADAM Proteins ADAM17 Protein Animals Biological and medical sciences Brain - metabolism Brain - physiopathology Cerebral Infarction - metabolism Cerebral Infarction - pathology Infarction, Middle Cerebral Artery - metabolism Infarction, Middle Cerebral Artery - physiopathology Ischemic Preconditioning Male Medical sciences Metalloendopeptidases - antagonists & inhibitors Metalloendopeptidases - metabolism Neurology Rats Rats, Inbred F344 Tumor Necrosis Factor-alpha - metabolism Up-Regulation Vascular diseases and vascular malformations of the nervous system |
| title | Upregulation of TACE/ADAM17 after ischemic preconditioning is involved in brain tolerance |
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