Apoptotic/mytogenic pathways during human heart development.
OBJECTIVE
The aim of our study was to assess myocytes apoptosis/mitosis and associated intracellular signalling pathways during heart development.


METHODS
Eight human fetal hearts (at different gestation ages) and seven human adult hearts were chosen as controls (five normal and two pathological) and studied from both a histological and a molecular point of view.


RESULTS
Our results are as follows: (i) all Shc isoforms are expressed and activated in the human fetal heart; (ii) a progressive fading of Shc and ERK expression are evident during gestation; (iii) JNK is present but it is not activated in the human fetal heart; (iv) CD95 is present in the first week of gestation and fades progressively; (v) apoptotic/proliferative processes are present in the early gestation phase and fades progressively; (vi) in the human heart, Shc isoform with medium weight is 55 kD and not 52 kD and it is upregulated in adult myocardial ischaemia.


CONCLUSIONS
Myocyte underwent apoptosis/mitosis during gestation. Shc isoforms, together with ERK maintain the homeostasis of the heart.
Department of Medicine, San Raffaele Scientific Institute (HSR), Milan, Via Olgettina 60, Milan 20132, Italy. paulo.fiorina@hsr.it
Paolo
P
Fiorina
Domenico
D
Corradi
Silvana
S
Pinelli
Roberta
R
Maestri
Costanza
C
Lagrasta
Mauro
M
Buscaglia
Alberto
A
Davalli
Franco
F
Folli
Ettore
E
Astorri
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D017209:Apoptosis; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005318:Fetal Heart / Q000378:metabolism / Q000473:pathology; D005865:Gestational Age; D006321:Heart / Q000196:embryology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019014:fas Receptor / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019014:fas Receptor; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases