Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected astrocytes

Na Liu, Virginia L. Scofield, Wenan Qiang, Mingshan Yan, Xianghong Kuang, Paul K.Y. Wong

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

The murine retrovirus, MoMuLV-ts1, induces progressive paralysis and immune deficiency in FVB/N mice. We have reported previously that ts1 infection causes apoptosis in astrocytes via endoplasmic reticulum (ER) and mitochondrial stress (Liu, N., Kuang, X., Kim, H.T., Stoica, G., Qiang, W., Scofield, V.L., Wong, P.K.Y. Wong. 2004. Possible involvement of both endoplasmic reticulum- and mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes. J. NeuroVirol. 10, 189-198). In the present study, we show that caspase 8 activation in these cells is mediated through ER stress-associated elevation of death receptor DR5 and the C/EBP homologous protein (GADD153/CHOP), an ER stress-initiated transcription factor, rather than through TNFα and TNF-R1 interactions on the cell surface. Treatment with Z-IETD-FMK, a specific inhibitor of caspase 8 enzymatic activity, reduced ER stress by two mechanisms: by inhibiting caspase 8 activation, and by preventing cleavage of the ER-associated membrane protein BAP31 into BAP20, which exacerbates the ER stress response. These findings suggest that caspase 8- and ER stress-associated apoptotic pathways are linked in ts1-infected astrocytes.

Original languageEnglish (US)
Pages (from-to)398-405
Number of pages8
JournalVirology
Volume348
Issue number2
DOIs
StatePublished - May 10 2006

Keywords

  • Apoptotic pathways
  • Astrocytes
  • BAP20
  • Caspase 8
  • DR5
  • Endoplasmic reticulum stress
  • GADD153/CHOP
  • Retrovirus

ASJC Scopus subject areas

  • Virology

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