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>> Românã
 
   
 

DANALACHE Bogdan Alexandru

Universite du Quebec, Montreal, Romania

Institution web page: http://www.uqam.ca
Personal web page: http://www3.sympatico.ca/amalia007
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Born: 1972

Interests: cells cluture, stem cells, regenerative medicine, cardiac, endocrinology

Details:
***
Oxytocin induces differentiation of P19 embryonic stem cells to
cardiomyocytes.
Paquin J, Danalache BA, Jankowski M, McCann SM, Gutkowska J.
Proc Natl Acad Sci U S A. 2002 Jul 9; 99(14): 9550-9555. published online before
print July 1, 2002
PMCID: 123178

We recently discovered the existence of the oxytocin/oxytocin receptor (OT/OTR) system in the heart. Activation of cardiac OTR stimulates the release of atrial natriuretic peptide (ANP), which is involved in regulation of blood pressure and cell growth. Having observed elevated OT levels in the fetal and newborn heart at a stage of intense cardiomyocyte hyperplasia, we hypothesized a role for OT in cardiomyocyte differentiation. We used mouse P19 embryonic stem cells to substantiate this potential role. P19 cells give rise to the formation of cell derivatives of all germ layers. Treatment of P19 cell aggregates with dimethyl sulfoxide (DMSO) induces differentiation to cardiomyocytes. In this work, P19 cells were allowed to aggregate from day 0 to day 4 in the presence of 0.5% DMSO, 10−7 M OT and/or 10−7 M OT antagonist (OTA), and then cultured in the absence of these factors until day 14. OT alone stimulated the production of beating cell colonies in all 24 independently growing cultures by day 8 of the differentiation protocol, whereas the same result was obtained in cells induced by DMSO only after 12 days. Cells induced with OT exhibited increased ANP mRNA, had abundant mitochondria (i.e., they strongly absorbed rhodamine 123), and expressed sarcomeric myosin heavy chain and dihydropyridine receptor-α1, confirming a cardiomyocyte phenotype. In addition, OT as well as DMSO increased OTR protein and OTR mRNA, and OTA completely inhibited the formation of cardiomyocytes in OT- and DMSO-supplemented cultures. These results suggest that the OT/OTR system plays an important role in cardiogenesis by promoting cardiomyocyte differentiation.
***
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13074-9. Epub 2004 Aug 17.

Oxytocin in cardiac ontogeny.

Jankowski M, Danalache B, Wang D, Bhat P, Hajjar F, Marcinkiewicz M, Paquin J,
McCann SM, Gutkowska J.

Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Hotel-Dieu,
3840 Rue Saint-Urbain, Montreal, QC, Canada H2W 1T8.

Previous studies demonstrated the presence of oxytocin (OT) and oxytocin
receptors (OTRs) in the heart. The present work provides results supporting a
potential role of OT in cardiomyogenesis. Here, we show a maximal OT and OTR
protein level in the developing rat heart at day 21 of gestation and postnatal
days 1-4, when cardiac myocytes are at a stage of intense hyperplasia. Between
postnatal days 1 and 66, OT decreased linearly in all heart chambers (4.1- to
6.6-fold). Correspondingly, immunocytochemistry demonstrated that OTRs, which
were eminent in postnatal cardiomyocytes, declined with age to low levels in
adults. Interestingly, in coronary vasculature, OTRs developed in endothelial
cells at postnatal days 12 and 22 and achieved a plateau in adult rats. These
findings suggest that OT can be involved in developmental formation of the
coronary vessels. In vivo, the OT/OTR system in the fetal heart was sensitive to
the actions of retinoic acid (RA), recognized as a major cardiac morphogen. RA
treatment produced a significant increase (2- to 3-fold) both in the OT
concentration and in the OT mRNA levels. Ex vivo, an OT antagonist inhibited
RA-mediated cardiomyocyte differentiation of P19 embryonic stem cells. The
decline of cardiac OT expression from infancy to adulthood of the rat and
changes in cell types expressing OTR indicate a dynamic regulation of the OT
system in the heart rather than constitutive expression. The results support the
hypothesis that RA induces cardiomyogenesis by activation of the cardiac OT
system. Copyright 2004 The National Academy of Sciencs of the USA

Selected publications:
• Jankowski M, Danalache B, Wang D, Bhat P, Hajjar F, Marcinkiewicz M, Paquin J, McCann SM, Gutkowska J. . Oxytocin in cardiac ontogeny. . Proc Natl Acad Sci U S A. , 101(35), pp. 13074-9, 2004.
• Paquin J, Danalache BA, Jankowski M, McCann SM, Gutkowska J. . Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. . Proc Natl Acad Sci U S A. , 99(14), pp. 9550-5., 2002.


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