NF‐κB and ERK cooperate to stimulate DNA synthesis by inducing ornithine decarboxylase and nitric oxide synthase in cardiomyocytes treated with TNF and LPS

FEBS Letters

Fattori, Monia¹  Pignatti, Carla¹  Clô, Carlo³  Flamigni, Flavio¹  Menegazzi, Marta²  Tantini, Benedetta¹  Giordano, Emanuele¹  Stefanelli, Claudio¹  Caldarera, Claudio Marcello¹ 

[1] Department of Biochemistry ‘G. Moruzzi’, School of Medicine, University of Bologna, via Irnerio 48, 40126 Bologna, Italy;Institute of Biological Chemistry, University of Verona, 37134 Verona, Italy;Institute of Biological Chemistry, School of Medicine, University of Parma, 43100 Parma, Italy

关键词: Tumor necrosis factor-α;    Lipopolysaccharide;    Nuclear factor-κB;    Extracellular signal-regulated kinase;    DNA synthesis;    Cardiomyocyte;    CM;    cardiomyocyte;    DFMO;    α-difluoromethylornithine;    ERK;    extracellular signal-regulated kinase;    I-κB;    inhibitor protein;    LLL;    n-acetylleucilleucinal;    L-NMMA;    N G-monomethylarginine;    LPS;    lipopolysaccharide;    MAPK;    mitogen-activated protein kinase;    NO;    nitric oxide;    NOS;    nitric oxide synthase;    NF-κB;    nuclear factor-κB;    ODC;    ornithine decarboxylase;    PDTC;    pyrrolidine dithiocarbamate;    STS;    staurosporine;    TNF;    tumor necrosis factor-α;   

DOI  :  10.1016/S0014-5793(02)02222-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We previously reported that tumor necrosis factor-α (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-κB (NF-κB) in the induction of nitric oxide synthase (NOS) and ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis. In addition NF-κB 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-κB activation. In conclusion, these results indicate that NF-κB, 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.

【 授权许可】

Unknown