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Abstract:

Chronic arsenic exposure is associated with increased morbidity and mortality for cardiovascular diseases. Arsenic increases myocardial infarction mortality in young adulthood, suggesting that exposure during foetal life correlates with cardiac alterations emerging later. Here, we investigated the mechanisms of arsenic trioxide (ATO) cardiomyocytes disruption during their differentiation from mouse embryonic stem cells. Throughout 15 days of differentiation in the presence of ATO (0.1, 0.5, 1.0 1/4M) we analysed: the expression of i) marker genes of mesoderm (day 4), myofibrillogenic commitment (day 7) and post-natal-like cardiomyocytes (day 15); ii) sarcomeric proteins and their organisation; iii) Connexin 43 and iv) the kinematics contractile properties of syncytia. The higher the dose used, the earlier the stage of differentiation affected (mesoderm commitment, 1.0 1/4M). At 0.5 or 1.0 1/4M the expression of cardiomyocyte marker genes is altered. Even at 0.1 1/4M, ATO leads to reduction and skewed ratio of sarcomeric proteins and to a rarefied distribution of Connexin 43 cardiac junctions. These alterations contribute to the dysruption of the sarcomere and syncytium organisation and to the impairment of kinematic parameters of cardiomyocyte function. This study contributes insights into the mechanistic comprehension of cardiac diseases caused by in utero arsenic exposure.

Registro:

Documento: Artículo
Título:Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
Autor:Rebuzzini, P.; Cebral, E.; Fassina, L.; Alberto Redi, C.; Zuccotti, M.; Garagna, S.
Filiación:Laboratorio di Biologia Dello Sviluppo, Dipartimento di Biologia e Biotecnologie Lazzaro Spallanzani, Università Degli Studi di Pavia, Pavia, Italy
Center for Health Technologies (CHT), Università of Pavia, Via Ferrata 1, Italy
Laboratorio de Reproducción y Fisiopatología Materno-Embrionaria, Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Dipartimento di Ingegneria Industriale e Dell Informazione, Università Degli Studi di Pavia, Pavia, Italy
Centro Ricerche di Medicina Rigenerativa, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Unita di Anatomia, Istologia Ed Embriologia, Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Università Degli Studi di Parma, Parma, Italy
Palabras clave:actinin; antineoplastic agent; arsenic trioxide; Brachyury protein; connexin 43; fetoprotein; homeobox protein Nkx-2.5; homeodomain protein; Nkx2-5 protein, mouse; organoarsenic derivative; oxide; T box transcription factor; transcription factor; transcription factor GATA 4; troponin C; troponin T; animal; biomechanics; cardiac muscle cell; cell differentiation; cell line; drug effects; fluorescent antibody technique; gene expression; genetics; metabolism; mouse; mouse embryonic stem cell; multicellular spheroid; reverse transcription polymerase chain reaction; sarcomere; time factor; Western blotting; Actinin; Animals; Antineoplastic Agents; Arsenicals; Biomechanical Phenomena; Blotting, Western; Cell Differentiation; Cell Line; Connexin 43; Fetal Proteins; Fluorescent Antibody Technique; GATA4 Transcription Factor; Gene Expression; Homeobox Protein Nkx-2.5; Homeodomain Proteins; Mice; Mouse Embryonic Stem Cells; Myocytes, Cardiac; Oxides; Reverse Transcriptase Polymerase Chain Reaction; Sarcomeres; Spheroids, Cellular; T-Box Domain Proteins; Time Factors; Transcription Factors; Troponin C; Troponin T
Año:2015
Volumen:5
DOI: http://dx.doi.org/10.1038/srep14993
Título revista:Scientific Reports
Título revista abreviado:Sci. Rep.
ISSN:20452322
CAS:arsenic trioxide, 1303-24-8, 1327-53-3, 13464-58-9, 15502-74-6; oxide, 16833-27-5; troponin C, 56094-11-2; troponin T, 60304-72-5; Actinin; Antineoplastic Agents; arsenic trioxide; Arsenicals; Brachyury protein; Connexin 43; Fetal Proteins; GATA4 Transcription Factor; Homeobox Protein Nkx-2.5; Homeodomain Proteins; Nkx2-5 protein, mouse; Oxides; T-Box Domain Proteins; Transcription Factors; Troponin C; Troponin T
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v5_n_p_Rebuzzini

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Citas:

---------- APA ----------
Rebuzzini, P., Cebral, E., Fassina, L., Alberto Redi, C., Zuccotti, M. & Garagna, S. (2015) . Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes. Scientific Reports, 5.
http://dx.doi.org/10.1038/srep14993
---------- CHICAGO ----------
Rebuzzini, P., Cebral, E., Fassina, L., Alberto Redi, C., Zuccotti, M., Garagna, S. "Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes" . Scientific Reports 5 (2015).
http://dx.doi.org/10.1038/srep14993
---------- MLA ----------
Rebuzzini, P., Cebral, E., Fassina, L., Alberto Redi, C., Zuccotti, M., Garagna, S. "Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes" . Scientific Reports, vol. 5, 2015.
http://dx.doi.org/10.1038/srep14993
---------- VANCOUVER ----------
Rebuzzini, P., Cebral, E., Fassina, L., Alberto Redi, C., Zuccotti, M., Garagna, S. Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes. Sci. Rep. 2015;5.
http://dx.doi.org/10.1038/srep14993