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R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome

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dc.contributor.author Mesquita, Fernanda C.P.
dc.contributor.author Arantes, Paulo C.
dc.contributor.author Kasai-Brunswick, Tais Hanae
dc.contributor.author Araujo, Dayana S.
dc.contributor.author Gubert, Fernanda
dc.contributor.author Monnerat, Gustavo
dc.contributor.author Silva dos Santos, Danúbia
dc.contributor.author Neiman, Gabriel
dc.contributor.author Leitão, Isabela C.
dc.contributor.author Barbosa, Raiana A. Q.
dc.contributor.author Coutinho, Jorge L.
dc.contributor.author Vaz, Isadora M.
dc.contributor.author dos Santos, Marcus N.
dc.contributor.author Borgonovo, Tamara
dc.contributor.author Cruz, Fernando E. S.
dc.contributor.author Miriuka, Santiago Gabriel
dc.contributor.author Medei, Emiliano H.
dc.contributor.author Campos de Carvalho, Antonio C.
dc.contributor.author Carvalho, Adriana B.
dc.date.accessioned 2020-10-21T15:54:33Z
dc.date.available 2020-10-21T15:54:33Z
dc.date.issued 2019-12-16
dc.identifier.citation Mesquita, F.C.P., Arantes, P.C., Kasai-Brunswick, T.H., Araujo, D.S., Gubert, F., Monnerat, G., Silva dos Santos, D., Neiman, G., Leitão, I.C., Barbosa, R.A.Q., Coutinho, J.L., Vaz, I.M., dos Santos, M.N., Borgonovo, T., Cruz, F.E.S., Miriuka, S., Medei, E.H., Campos de Carvalho, A.C., Carvalho, A.B. R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome. Sci Rep. 2019 Dec 16;9(1):19203. doi: 10.1038/s41598-019-55837-w en_US
dc.identifier.uri https://doi.org/10.1038/s41598-019-55837-w
dc.identifier.uri https://repositorio.fleni.org.ar/handle/123456789/208
dc.description.abstract Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The objective of this work was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C > T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the IKr inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of IKr on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane. en_US
dc.language.iso eng en_US
dc.publisher Nature Publishing Group en_US
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/2.5/ar/
dc.subject Myocytes, Cardiac en_US
dc.subject Miocitos Cardíacos en_US
dc.subject Pluripotent Stem Cells en_US
dc.subject Células Madre Pluripotentes en_US
dc.title R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome en_US
dc.type info:eu-repo/semantics/publishedVersion
dc.type info:eu-repo/semantics/article en_US
dc.description.fil Fil: Mesquita, Fernanda C.P. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Arantes, Paulo C. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Kasai-Brunswick, Tais Hanae. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Araujo, Dayana S. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Gubert, Fernanda. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Monnerat, Gustavo. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Silva dos Santos, Danúbia. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Neiman, Gabriel. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Leitão, Isabela C. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Barbosa, Raiana A. Q. Federal University of Rio de Janeiro; Brasil.
dc.description.fil Fil: Coutinho, Jorge L. National Institute of Cardiology; Brasil.
dc.description.fil Fil: Vaz, Isadora M. Pontifical Catholic University of Parana; Brasil.
dc.description.fil Fil: dos Santos, Marcus N. Carlos Chagas Filho Institute of Biophysics; Brasil.
dc.description.fil Fil: Borgonovo, Tamara. Pontifical Catholic University of Parana; Brasil.
dc.description.fil Fil: Cruz, Fernando E. S. National Institute of Cardiology; Brasil.
dc.description.fil Fil: Miriuka, Santiago Gabriel. Fleni. Laboratorio de Investigación Aplicada a las Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.
dc.description.fil Fil: Medei, Emiliano H. Carlos Chagas Filho Institute of Biophysics; Brasil.
dc.description.fil Fil: Campos de Carvalho, Antonio C. Carlos Chagas Filho Institute of Biophysics; Brasil.
dc.description.fil Fil: Carvalho, Adriana B. Carlos Chagas Filho Institute of Biophysics; Brasil.
dc.relation.ispartofVOLUME 9
dc.relation.ispartofNUMBER 1
dc.relation.ispartofPAGINATION 19203
dc.relation.ispartofCOUNTRY Reino Unido
dc.relation.ispartofCITY Londres
dc.relation.ispartofTITLE Scientific reports
dc.relation.ispartofISSN 2045-2322
dc.type.snrd info:ar-repo/semantics/artículo es_ES


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