Tumour necrosis factor-related apoptosis-inducing ligand sequentially activates pro-survival and pro-apoptotic pathways in SK-N-MC neuronal cells

Daniela Milani, Giorgio Zauli, Erika Rimondi, Claudio Celeghini, Sandra Marmiroli, Paola Narducci, Silvano Capitani, Paola Secchiero

Research output: Contribution to journalArticlepeer-review

Abstract

The SK-N-MC neuroblastoma cell line, which expresses surface tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors TRAIL-R2 and TRAIL-R4, was used as a model system to examine the effect of TRAIL on key intracellular pathways involved in the control of neuronal cell survival and apoptosis. TRAIL induced distinct short-term (1-60 min) and long-term (3-24 h) effects on the protein kinase B (PKB)/Akt (Akt), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), nuclear factor kappa B (NF-κB) and caspase pathways. TRAIL rapidly (from 20 min) induced the phosphorylation of Akt and ERK, but not of c-Jun NH2-terminal kinase (JNK). Moreover, TRAIL increased CREB phosphorylation and phospho-CREB DNA binding activity in a phosphatidylinositol 3-kinase (PI 3K)/Akt-dependent manner. At later time points (from 3 to 6 h onwards) TRAIL induced a progressive degradation of inhibitor of κB (IκB)β and IκBα, but not IκBα, coupled to the nuclear translocation of NF-κB and an increase in its DNA binding activity. In the same time frame, TRAIL started to activate caspase-8 and caspase-3, and to induce apoptosis. Remarkably, caspase-dependent cleavage of NF-κB family members as well as of Akt and CREB proteins, but not of ERK, became prominent at 24 h, a time point coincident with the peak of caspase-dependent apoptosis.

Original languageEnglish
Pages (from-to)126-135
Number of pages10
JournalJournal of Neurochemistry
Volume86
Issue number1
DOIs
Publication statusPublished - Jul 2003

Keywords

  • CAMP response element-binding protein
  • Caspases
  • Neuroblastoma cells
  • Nuclear factor kappa B
  • Protein kinase B (Akt)
  • Tumour necrosis factor-related apoptosis-inducing ligand

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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