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dc.contributor.author
He, Xiju
dc.contributor.author
Li, Shoutian
dc.contributor.author
Liu, Benju
dc.contributor.author
Susperreguy, Sebastian
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Formoso, Karina
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Yao, Jinghong
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Kang, Jinsong
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Shi, Anbing
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Liao, Yanhong
dc.date.available
2018-06-19T17:16:09Z
dc.date.issued
2017-05
dc.identifier.citation
He, Xiju; Li, Shoutian; Liu, Benju; Susperreguy, Sebastian; Formoso, Karina; et al.; Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 114; 23; 5-2017; 1-10
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/49310
dc.description.abstract
The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase. Working in vitro with H9c2 cardiomyoblasts subjected to 9-h hypoxia followed by 6-h reoxygenation (H/R), and analyzing changes occurring in areas-at-risk (AARs) of murine hearts subjected to a 30-min ischemia followed by 24-h reperfusion (I/R) protocol, we found: (<i>i</i>) that blocking TRPC with SKF96365 significantly ameliorated damage induced by H/R, including development of the mitochondrial permeability transition and proapoptotic changes in Bcl2/BAX ratios; and (<i>ii</i>) that AAR tissues had increased TUNEL<sup>+</sup> cells, augmented Bcl2/BAX ratios, and increased p(S240)NFATc3, p(S473)AKT, p(S9)GSK3β, and TRPC3 and -6 proteins, consistent with activation of a positive-feedback loop in which calcium entering through TRPCs activates calcineurin-mediated NFATc3-directed transcription of TRPC genes, leading to more Ca<sup>2+</sup> entry. All these changes were markedly reduced in mice lacking TRPC3, -6, and -7. The changes caused by I/R in AAR tissues were matched by those seen after H/R in cardiomyoblasts in all aspects except for p-AKT and p-GSK3β, which were decreased after H/R in cardiomyoblasts instead of increased. TRPC should be promising targets for pharmacologic intervention after cardiac infarcts.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Trpc
dc.subject
Hipoxia
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Cardiac Infarct
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Reperfusion
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Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Major contribution of the 3/6/7 class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-07T14:11:20Z
dc.journal.volume
114
dc.journal.number
23
dc.journal.pagination
1-10
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: He, Xiju. Huazhong University Of Science And Technology; China
dc.description.fil
Fil: Li, Shoutian. Huazhong University Of Science And Technology; China
dc.description.fil
Fil: Liu, Benju. Huazhong University Of Science And Technology; China
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Fil: Susperreguy, Sebastian. Pontificia Universidad Católica Argentina ; Argentina
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Fil: Formoso, Karina. Pontificia Universidad Católica Argentina ; Argentina
dc.description.fil
Fil: Yao, Jinghong. Huazhong University Of Science And Technology; China
dc.description.fil
Fil: Kang, Jinsong. Huazhong University Of Science And Technology; China
dc.description.fil
Fil: Shi, Anbing. Huazhong University Of Science And Technology; China
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
dc.description.fil
Fil: Liao, Yanhong. Huazhong University Of Science And Technology; China
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1073/pnas.1621384114
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/114/23/E4582
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