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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-4-18
pubmed:abstractText
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 ?-actinin, ?-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1879-3169
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
10
pubmed:volume
202
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
226-36
pubmed:meshHeading
pubmed-meshheading:21354282-Adenosine Triphosphate, pubmed-meshheading:21354282-Animals, pubmed-meshheading:21354282-Cell Differentiation, pubmed-meshheading:21354282-Cell Line, pubmed-meshheading:21354282-Down-Regulation, pubmed-meshheading:21354282-Embryoid Bodies, pubmed-meshheading:21354282-Embryonic Stem Cells, pubmed-meshheading:21354282-Environmental Pollutants, pubmed-meshheading:21354282-Enzymes, pubmed-meshheading:21354282-Gene Expression Regulation, Enzymologic, pubmed-meshheading:21354282-Metabolic Detoxication, Phase I, pubmed-meshheading:21354282-Metabolic Detoxication, Phase II, pubmed-meshheading:21354282-Mice, pubmed-meshheading:21354282-Microscopy, Electron, Transmission, pubmed-meshheading:21354282-Myocytes, Cardiac, pubmed-meshheading:21354282-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:21354282-Teratogens, pubmed-meshheading:21354282-Tetrachlorodibenzodioxin, pubmed-meshheading:21354282-Transcription, Genetic
pubmed:year
2011
pubmed:articleTitle
The differentiation of cardiomyocytes from mouse embryonic stem cells is altered by dioxin.
pubmed:affiliation
Laboratorio di Biologia dello Sviluppo, Dipartimento di Biologia Animale, Universita' degli Studi di Pavia, Via Ferrata 9, 27100 Pavia, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't