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

Miriam Mangelus, Ronit Galron, Zvi Naor, Mordechai Sokolovsky

Research output: Contribution to journalArticlepeer-review

Abstract

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
Volume21
Issue number6
DOIs
StatePublished - 2001

Keywords

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

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