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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 |