Adenylyl cyclase activity and gene expression during mesodermal differentiation of the P19 embryonal carcinoma cells.
DMSO-primed P19 pluripotent cells, which recapitulate the first stages of mammalian cardiogenesis and endodermal formation, were used as an in vitro model to analyze the variations in activity and expression of the different adenylyl cyclase (AC) isoforms during the early events of embryonic cell differentiation. Here, we show that the total AC activity, which increases up to 10-fold after differentiation of P19 cells, is mainly associated with increases in AC2, AC5, and AC6 mRNA levels. Particularly, the marked increase in AC5 mRNA correlates with the appearance of beating cardiomyocytes and with the transcription of the atrial myosin light chain (MLC1A) gene which encodes a protein specifically involved in the cardiac muscle cell contractile phenotype. Together, the results strongly suggest that 1) a rise in cyclic AMP (cAMP) may be associated with cardiomyocyte and endodermal cell differentiation during mammalian embryogenesis; and 2) AC5 gene expression starts very early during normal mouse cardiogenesis and correlates with the differentiation of cardiomyocytes.
Lipskaia
L
L
Institut National de la Santé et de la Recherche Médicale U-99, Hôpital Henri Mondor, Créteil, France.
Grépin
C
C
Defer
N
N
Hanoune
J
J
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D050991:GATA4 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006321:Heart / Q000196:embryology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007633:Keratins / Q000235:genetics; D051379:Mice; D018994:Myosin Light Chains / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D007527:Isoenzymes; D018994:Myosin Light Chains; D012333:RNA, Messenger; D013449:Sulfonamides; D014157:Transcription Factors; C076659:myosin light chain I; D005576:Colforsin; C017967:W 7; D007633:Keratins; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D002118:Calcium; D004121:Dimethyl Sulfoxide