Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: Induction of caspase-dependent cell death and activation of NF-κB

Zulfiqar Cheema, Stephen B. Wade, Masataka Sata, Kenneth Walsh, Farida Sohrabji, Rajesh C. Miranda

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

The developing cerebral cortex undergoes a period of substantial cell death. The present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in cerebral cortical development. Fas mRNA and protein are transiently expressed in subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE- inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD, RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-κB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL- expressing) cells and that Fas may have functions in addition to suicide in the developing brain.

Original languageEnglish (US)
Pages (from-to)1754-1770
Number of pages17
JournalJournal of Neuroscience
Volume19
Issue number5
StatePublished - Mar 1 1999
Externally publishedYes

Fingerprint

Caspases
Cerebral Cortex
Fas Ligand Protein
Cell Death
Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein
Receptor-Interacting Protein Serine-Threonine Kinases
Suicide
CD95 Antigens
Proteins
Transcription Factor RelA
Death Domain Receptors
Brain
Nucleic Acids
Anti-Idiotypic Antibodies
Down-Regulation
Cell Count
Messenger RNA

Keywords

  • BrdU
  • CNS
  • FADD
  • FasL
  • FLIP
  • ICE protease inhibitors
  • Interleukin-1β-converting enzyme
  • PCNA
  • Rat
  • RIP

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex : Induction of caspase-dependent cell death and activation of NF-κB. / Cheema, Zulfiqar; Wade, Stephen B.; Sata, Masataka; Walsh, Kenneth; Sohrabji, Farida; Miranda, Rajesh C.

In: Journal of Neuroscience, Vol. 19, No. 5, 01.03.1999, p. 1754-1770.

Research output: Contribution to journalArticle

Cheema, Zulfiqar ; Wade, Stephen B. ; Sata, Masataka ; Walsh, Kenneth ; Sohrabji, Farida ; Miranda, Rajesh C. / Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex : Induction of caspase-dependent cell death and activation of NF-κB. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 5. pp. 1754-1770.
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AU - Sata, Masataka

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