Fas-mediated apoptosis in a rat acinar cell line is dependent on caspase-1 activity

Sonomi Aiba-Masago, Rejei Masago, Norma Vela-Roch, Norman Talal, Howard Dang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Apoptosis plays an important role in the dysfunction of exocrine glands. Fas is a death-inducing receptor found on many types of cells including epithelial acinar cells. To elucidate the intracellular mechanism of Fas-mediated cell death in exocrine glands, an epithelial acinar cell line, SMG-C6, was studied. Caspase-1, -3, -8, and -9 activities were elevated in SMG-C6 cells after the induction of apoptosis by soluble Fas ligand (FasL). The activation of caspase-1 and -8 occurred prior to caspase-3 and -9 activation. The caspase-1 inhibitor, zYVAD-fmk, was effective in preventing cell death, whereas the caspase-3 and -8 inhibitors (ac-DEVD-CHO and ac-IETD-CHO, respectively) were not. zYVAD-fmk was able to inhibit caspase-3 activation indicating that caspase-1 is upstream to caspase-3. Furthermore, kinetic studies show that caspase-1 is an early event in the Fas apoptotic pathway. This study shows that caspase-1 participates in Fas-mediated apoptosis of epithelial cells by initiating the caspase cascade.

Original languageEnglish (US)
Pages (from-to)617-624
Number of pages8
JournalCellular Signalling
Volume13
Issue number9
DOIs
StatePublished - Aug 20 2001

Keywords

  • Apoptosis
  • CD95 caspase
  • Epithelial cells
  • Salivary gland
  • Sjögren's syndrome

ASJC Scopus subject areas

  • Cell Biology

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