P. Rouet-benzineb et al., Angiotensin II induces nuclear factor-kappa B activation in cultured neonatal rat cardiomyocytes through protein kinase C signaling pathway, J MOL CEL C, 32(10), 2000, pp. 1767-1778
Rat neonatal ventricular cardiomyocytes (RNVM) possess G protein-coupled AT
(1) receptors for angiotensin II (AngII) that activate multiple intracellul
ar pathways. To elucidate potential signaling mechanisms involved, we focus
sed on the nuclear transcription factor-kappa B (NF-kappaB) in RNVM culture
. Using specific antibody to NF-kappa Bp65, immunolocalization of NF-kappaB
was cytoplasmic in unstimulated cardiomyocytes, whereas NF-kappaB was tran
slocated into the RNVM nucleus in response to AngII. This translocation was
inhibited in the presence of calphostin C, a specific inhibitor of protein
kinase C (PKC). Western blot analysis showed an increase of NF-kappaB in A
ngII-stimulated cardiomyocyte nuclear extracts as compared to controls, Bio
molecular interaction analysis (BIA analysis) of NF-kappaB activation showe
d that only AngII-nuclear extracts bound to NF-kappaB consensus sequence wi
th a high degree of affinity. This DNA-binding capacity was completely lost
in calphostin C-treated cells. At transcriptional level in RNVM, AngII med
iates the upregulation of matrix gelatinase (MMP-9), which is totally inhib
ited by calphostin C treatment. In conclusion, cardiomyocyte nuclear NF-kap
paB translocation in response to Ang II via PKC pathway activates cardiomyo
cyte-specific transcription of MMP-9 and may activate transcription From re
sponsive genes which are involved in cardiac hypertrophy process and/or car
diac remodeling. (C) 2000 Academic Press.