Absence of caspase 8 and high expression of PED protect primitive neural cells from cell death

Lucia Ricci-Vitiani, Francesca Pedini, Cristiana Mollinari, Gerolama Condorelli, Désirée Bonci, Alessandra Bez, Augusto Colombo, Eugenio Parati, Cesare Peschle, Ruggero De Maria

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms that control neural stem and progenitor cell survival are unknown. In several pathological conditions, death receptor (DR) ligands and inflammatory cytokines exert a deleterious effect on neurons, whereas primitive neural cells migrate and survive in the site of lesion. Here, we show that even in the presence of inflammatory cytokines, DRs are unable to generate death signals in primitive neural cells. Neural stem and progenitor cells did not express caspase 8, the presence of which is required for initiating the caspase cascade. However, exogenous or cytokine-mediated expression of caspase 8 was not sufficient to restore their DR sensitivity. Searching for molecules potentially able to block DR death-inducing signaling complex (DISC), we found that primitive neural cells expressed high levels of the death effector domain-containing protein PED (also known as PEA-15). PED localized in the DISC and prevented caspase 8 recruitment and activation. Moreover, lentiviral-mediated delivery of PED antisense DNA resulted in dramatic down-regulation of the endogenous gene expression and sensitization of primitive neural cells to apoptosis mediated by inflammatory cytokines and DRs. Thus, absence of caspase 8 and high expression of PED constitute two levels of protection from apoptosis induced by DRs and inflammatory cytokines in neural stem and progenitor cells.

Original languageEnglish
Pages (from-to)1257-1266
Number of pages10
JournalJournal of Experimental Medicine
Volume200
Issue number10
DOIs
Publication statusPublished - Nov 15 2004

Keywords

  • Apoptosis
  • Death receptors
  • Death-inducing signaling complex
  • Inflammatory cytokines
  • Neural stem cells

ASJC Scopus subject areas

  • Immunology

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