NF-kappaB signaling blockade by Bay 11-7085 during early cardiac morphogenesis induces alterations of the outflow tract in chicken heart.
Nuclear factor kappaB (NF-kappaB) is a pleiotropic transcription factor implicated in the regulation of diverse morphologic cardiac alterations, for which the p50 and p65 subunits form the most prevalent dimeric form in the heart. NF-kappaB is inactivated by proteins of the IkappaB family, which trap it in the cytoplasm. It is not known whether NF-kappaB influences cardiac development.


OBJECTIVE
Here we investigated the role of NF-kappaB in regulating transcription in chicken heart morphogenesis. Specifically, we tested whether NF-kappaB activation is required for normal formation of the outflow tract (OFT) during a critical stage of heart development.


RESULTS
We designed a reporter vector with kappaB binding sites for Rel family members in the promoter, upstream from the cDNA of Green Fluorescent Protein (GFP). This construct was injected directly into the developing heart of chicken embryos. NF-kappaB activation was subsequently inhibited by administration of the specific pharmacological agent Bay 11-7085. We found that forced NF-kappaB expression was associated with multiple congenital cardiac alterations of the OFT (mainly IVC, DORV and great arteries stenosis).


CONCLUSIONS
These findings indicate that blockade of NF-kappaB induces apoptosis and is an important factor in the development of OFT during cardiogenesis. However, it remains unknown which members of the Rel family are relevant in this process.
Hernández-Gutierrez
S
S
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, México D.F., 04510.
García-Peláez
I
I
Zentella-Dehesa
A
A
Ramos-Kuri
M
M
Hernández-Franco
P
P
Hernández-Sánchez
F
F
Rojas
E
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013450:Sulfones / Q000494:pharmacology*; D013723:Teratogens / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C416282:BAY 11-7085; D016895:Culture Media, Serum-Free; D016328:NF-kappa B; D009570:Nitriles; D013450:Sulfones; D013723:Teratogens; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins