Abstract
2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) causes abnormalities during heart development. Cardiomyocytes derived from embryonic stem (ES) cells are a robust model for the study of early cardiomyogenesis. Here, we evaluated the effects of TCDD at key stages during the differentiation of mouse ES cells into cardiomyocytes analysing: (i) the transcription of lineage differentiation (Brachyury, Nkx-2.5, Actc-1), cardiac-specific (Alpk3, cTnT, cTnI, cTnC) and detoxification phase I (Cyp1A1, Cyp1A2 and Cyp1B1) and phase II (Nqo1, Gsta1 and Ugt1a6) genes; (ii) the global gene expression; (iii) the ultrastructure of ES-derived cardiomyocytes; (iv) level of ATP production and (v) the immunolocalisation of sarcomeric α-actinin, β-myosin heavy chain and cTnT proteins. We show that TCDD affects the differentiation of ES cells into cardiomyocytes at several levels: (1) induces the expression of phase I genes; (2) down-regulates a group of heart-specific genes, some involved in the oxidative phosphorylation pathway; (3) reduces the efficiency of differentiation; (4) alters the arrangement of mitochondria, that show twisted and disrupted cristae, and of some sarcomeres, with misalignement or disarrangement of the myofibrillar organisation and (5) reduces ATP production. This study provides novel evidences that TCDD impairs cardiomyocyte differentiation. Sarcomeres and mitochondria could be a target for dioxin toxicity, their disruption representing a possible mechanism developing cardiac injury.
| Original language | English |
|---|---|
| Pages (from-to) | 226-236 |
| Number of pages | 11 |
| Journal | Toxicology Letters |
| Volume | 202 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 10 2011 |
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Keywords
- Cardiomyocytes differentiation
- Dioxin
- Embryonic stem cells
- Mouse
- Myofibrils
ASJC Scopus subject areas
- Toxicology
Cite this
The differentiation of cardiomyocytes from mouse embryonic stem cells is altered by dioxin. / Neri, Tui; Merico, Valeria; Fiordaliso, Fabio; Salio, Monica; Rebuzzini, Paola; Sacchi, Lucia; Bellazzi, Riccardo; Redi, Carlo Alberto; Zuccotti, Maurizio; Garagna, Silvia.
In: Toxicology Letters, Vol. 202, No. 3, 10.05.2011, p. 226-236.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The differentiation of cardiomyocytes from mouse embryonic stem cells is altered by dioxin
AU - Neri, Tui
AU - Merico, Valeria
AU - Fiordaliso, Fabio
AU - Salio, Monica
AU - Rebuzzini, Paola
AU - Sacchi, Lucia
AU - Bellazzi, Riccardo
AU - Redi, Carlo Alberto
AU - Zuccotti, Maurizio
AU - Garagna, Silvia
PY - 2011/5/10
Y1 - 2011/5/10
N2 - 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) causes abnormalities during heart development. Cardiomyocytes derived from embryonic stem (ES) cells are a robust model for the study of early cardiomyogenesis. Here, we evaluated the effects of TCDD at key stages during the differentiation of mouse ES cells into cardiomyocytes analysing: (i) the transcription of lineage differentiation (Brachyury, Nkx-2.5, Actc-1), cardiac-specific (Alpk3, cTnT, cTnI, cTnC) and detoxification phase I (Cyp1A1, Cyp1A2 and Cyp1B1) and phase II (Nqo1, Gsta1 and Ugt1a6) genes; (ii) the global gene expression; (iii) the ultrastructure of ES-derived cardiomyocytes; (iv) level of ATP production and (v) the immunolocalisation of sarcomeric α-actinin, β-myosin heavy chain and cTnT proteins. We show that TCDD affects the differentiation of ES cells into cardiomyocytes at several levels: (1) induces the expression of phase I genes; (2) down-regulates a group of heart-specific genes, some involved in the oxidative phosphorylation pathway; (3) reduces the efficiency of differentiation; (4) alters the arrangement of mitochondria, that show twisted and disrupted cristae, and of some sarcomeres, with misalignement or disarrangement of the myofibrillar organisation and (5) reduces ATP production. This study provides novel evidences that TCDD impairs cardiomyocyte differentiation. Sarcomeres and mitochondria could be a target for dioxin toxicity, their disruption representing a possible mechanism developing cardiac injury.
AB - 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) causes abnormalities during heart development. Cardiomyocytes derived from embryonic stem (ES) cells are a robust model for the study of early cardiomyogenesis. Here, we evaluated the effects of TCDD at key stages during the differentiation of mouse ES cells into cardiomyocytes analysing: (i) the transcription of lineage differentiation (Brachyury, Nkx-2.5, Actc-1), cardiac-specific (Alpk3, cTnT, cTnI, cTnC) and detoxification phase I (Cyp1A1, Cyp1A2 and Cyp1B1) and phase II (Nqo1, Gsta1 and Ugt1a6) genes; (ii) the global gene expression; (iii) the ultrastructure of ES-derived cardiomyocytes; (iv) level of ATP production and (v) the immunolocalisation of sarcomeric α-actinin, β-myosin heavy chain and cTnT proteins. We show that TCDD affects the differentiation of ES cells into cardiomyocytes at several levels: (1) induces the expression of phase I genes; (2) down-regulates a group of heart-specific genes, some involved in the oxidative phosphorylation pathway; (3) reduces the efficiency of differentiation; (4) alters the arrangement of mitochondria, that show twisted and disrupted cristae, and of some sarcomeres, with misalignement or disarrangement of the myofibrillar organisation and (5) reduces ATP production. This study provides novel evidences that TCDD impairs cardiomyocyte differentiation. Sarcomeres and mitochondria could be a target for dioxin toxicity, their disruption representing a possible mechanism developing cardiac injury.
KW - Cardiomyocytes differentiation
KW - Dioxin
KW - Embryonic stem cells
KW - Mouse
KW - Myofibrils
UR - http://www.scopus.com/inward/record.url?scp=79954572856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954572856&partnerID=8YFLogxK
U2 - 10.1016/j.toxlet.2011.02.008
DO - 10.1016/j.toxlet.2011.02.008
M3 - Article
C2 - 21354282
AN - SCOPUS:79954572856
VL - 202
SP - 226
EP - 236
JO - Toxicology Letters
JF - Toxicology Letters
SN - 0378-4274
IS - 3
ER -