Hormone‐activated nuclear receptors inhibit the stimulation of the JNK and ERK signalling pathways in endothelial cells

FEBS Letters

Jiménez, Benilde¹  Caelles, Carme²  González, Marı́a Victoria¹  González-Sancho, José Manuel¹  Munoz, Alberto¹ 

[1] Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Cientı́ficas, Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029 Madrid, Spain;Facultad de Farmacia, Universidad de Barcelona, E-08028 Barcelona, Spain

关键词: Glucocorticoid;    Retinoid;    JNK signalling;    ERK signalling;    Angiogenesis;    AP-1 antagonism;    CBP;    cyclic AMP response element binding protein binding protein;    DMEM;    Dulbecco's modified Eagle's medium;    ERK;    extracellular-regulated kinase;    FCS;    fetal calf serum;    GR;    glucocorticoid receptor;    JNK;    c-Jun N-terminal kinase;    RA;    retinoic acid;    RAR;    retinoic acid receptor;    TNF;    tumor necrosis factor;    TPA;    12-O-tetradecanoyl phorbol 13-acetate;    VEGF;    vascular endothelial growth factor;    vitD3;    vitamin D3;    VDR;    vitamin D receptor;   

DOI  :  10.1016/S0014-5793(99)01257-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Glucocorticoid hormones, retinoids, and vitamin D3 display anti-angiogenic activity in tumor-bearing animals. However, despite their in vivo effect on the tumor vasculature little is known about their mechanism of action. Here we show that the synthetic glucocorticoid dexamethasone (Dex) and retinoic acid (RA) inhibit the activation of c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK) signalling pathways by the pro-angiogenic agents tumor necrosis factor and vascular endothelial growth factor in endothelial cells. In contrast, Dex and RA failed to inhibit the activation of the p38 mitogen-activated protein kinase cascade. As a number of pro-angiogenic factors activate AP-1 transcription factor via the JNK and ERK pathways, our results suggest that the antagonism with AP-1 may underlie at least partially the anti-angiogenic effect of glucocorticoids and retinoids.

【 授权许可】

Unknown