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- Title
Tumour necrosis factor-related apoptosis-inducing ligand sequentially activates pro-survival and pro-apoptotic pathways in SK-N-MC neuronal cells.
- Authors
Milani, Daniela; Zauli, Giorgio; Rimondi, Erika; Celeghini, Claudio; Marmiroli, Sandra; Narducci, Paola; Capitani, Silvano; Secchiero, Paola
- Abstract
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 IκBε, 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.
- Subjects
PROTEIN kinases; NF-kappa B; NEUROBLASTOMA
- Publication
Journal of Neurochemistry, 2003, Vol 86, Issue 1, p126
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.01805.x