Involvement of nuclear factor-κB in endothelin-A-receptor-induced proliferation and inhibition of apoptosis

Miriam Mangelus, Ronit Galron, Zvi Naor, Mordechai Sokolovsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Endothelins have been implicated in the regulation of cell proliferation, differentiation, and apoptosis, but the mechanisms of these complex events are not yet fully understood. Although the nuclear factor-κB (NF-κB) was shown to play a prominent role in the above processes, its participation in endothelin receptor A (ETAR) signaling has not been previously demonstrated. This study provides evidence that NF-κB is involved in ETAR-induced proliferation and inhibition of apoptosis. Endothelin (ET)-1, ET-3, and sarafotoxin b induce cell proliferation and prevent apoptosis induced by serum deprivation in a Chinese hamster lung (CCL39) cell line that stably expresses ETAR (CCL39ETA). Activation of ETAR resulted in enhanced DNA-binding activity of NF-κB and degradation of IκB-α. Expression of the dominant negative form of IκB-α (IκBΔN) inhibited the proliferative activities mediated by ETAR as well as its antiapoptotic activities. Treatment of the cells with prostaglandin A1, an inhibitor of IκB kinase-β, reduced ET-1-induced proliferation and its antiapoptotic effect. These findings indicate that the regulation of cell proliferation and apoptosis by ETAR is mediated by the ETAR-activated NF-κB.

Original languageEnglish
Pages (from-to)657-674
Number of pages18
JournalCellular and Molecular Neurobiology
Issue number6
StatePublished - 2001


  • Apoptosis
  • Endothelin receptors
  • Endothelins
  • NF-κB
  • Proliferation
  • Sarafotoxins


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