NF-kappaB and ERK cooperate to stimulate DNA synthesis by inducing ornithine decarboxylase and nitric oxide synthase in cardiomyocytes treated with TNF and LPS.
We previously reported that tumor necrosis factor-alpha (TNF) and lipopolysaccharide (LPS) stimulate DNA synthesis in chick embryo cardiomyocytes (CM) via nitric oxide and polyamine biosynthesis. Here we show an involvement of nuclear factor-kappaB (NF-kappaB) in the induction of nitric oxide synthase (NOS) and ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis. In addition NF-kappaB activation appears to favor survival of CM by reducing caspase activation. TNF and LPS also stimulate phosphorylation of extracellular signal-regulated kinase (ERK), which is required for the changes in ODC and caspase activity, but not for NOS induction or NF-kappaB activation. In conclusion, these results indicate that NF-kappaB, in cooperation with ERK, plays a pivotal role in the growth stimulating effects of TNF and LPS, leading to the induction of both ODC and NOS and to the reduction of caspase activity.
Tantini
Benedetta
B
Department of Biochemistry 'G. Moruzzi', School of Medicine, University of Bologna, via Irnerio 48, 40126, Bologna, Italy. tantini@biocfarm.unibo.it
Pignatti
Carla
C
Fattori
Monia
M
Flamigni
Flavio
F
Stefanelli
Claudio
C
Giordano
Emanuele
E
Menegazzi
Marta
M
Clô
Carlo
C
Caldarera
Claudio Marcello
CM
D000818:Animals; D002455:Cell Division; D002642:Chick Embryo; D004790:Enzyme Induction; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008070:Lipopolysaccharides; D008934:Mitogens; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases; D009955:Ornithine Decarboxylase