Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes

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 m...

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Autores principales:	Rebuzzini, P., Cebral, E., Fassina, L., Alberto Redi, C., Zuccotti, M., Garagna, S.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_20452322_v5_n_p_Rebuzzini
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_20452322_v5_n_p_Rebuzzini2023-10-03T16:38:12Z Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes Rebuzzini, P. Cebral, E. Fassina, L. Alberto Redi, C. Zuccotti, M. Garagna, S. 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 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. Fil:Cebral, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_20452322_v5_n_p_Rebuzzini
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	JOUR
author	Rebuzzini, P. Cebral, E. Fassina, L. Alberto Redi, C. Zuccotti, M. Garagna, S.
author_facet	Rebuzzini, P. Cebral, E. Fassina, L. Alberto Redi, C. Zuccotti, M. Garagna, S.
author_sort	Rebuzzini, P.
title	Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
title_short	Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
title_full	Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
title_fullStr	Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
title_full_unstemmed	Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
title_sort	arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes
url	http://hdl.handle.net/20.500.12110/paper_20452322_v5_n_p_Rebuzzini
work_keys_str_mv	AT rebuzzinip arsenictrioxidealtersthedifferentiationofmouseembryonicstemcellintocardiomyocytes AT cebrale arsenictrioxidealtersthedifferentiationofmouseembryonicstemcellintocardiomyocytes AT fassinal arsenictrioxidealtersthedifferentiationofmouseembryonicstemcellintocardiomyocytes AT albertoredic arsenictrioxidealtersthedifferentiationofmouseembryonicstemcellintocardiomyocytes AT zuccottim arsenictrioxidealtersthedifferentiationofmouseembryonicstemcellintocardiomyocytes AT garagnas arsenictrioxidealtersthedifferentiationofmouseembryonicstemcellintocardiomyocytes
_version_	1782025990882459648

Arsenic trioxide alters the differentiation of mouse embryonic stem cell into cardiomyocytes

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