Possible involvement of both endoplasmic reticulum- and mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes

Na Liu, Xianghong Kuang, Hun Taek Kim, George Stoica, Wenan Qiang, Virginia Lee Scofield, Paul K Y Wong

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

The Moloney murine leukemia virus (MoMuLV)-ts1 retrovirus, a naturally occurring mutant of MoMuLV-TB, causes a neuroimmunodegenerative syndrome in mice. The authors show here that ts1 triggers apoptosis in immortalized astrocytes, C1 cells, and primary cultured astrocytes, and that this apoptosis is caused by endoplasmic reticulum (ER) stress resulting from accumulation of the viral envelope preprotein gPr80env. In ts1-infected C1 cells, an unfolded protein response was identified by activation of the ER-resident transmembrane protein kinase PERK, an event that leads to hyperphosphorylation of eIF2α, up-regulation of GRP78, increased amounts of GADD153/CHOP, and cleavage of procaspase-12. Up-regulation of GRP78 and cleavage of procaspase-12 were also detected in primary cultured astrocytes infected with ts1. In ts1-infected C1 cells, ER stress was followed by mitochondrial stress, detected as mitochondrial transmembrane potential dissipation, cleavage of procaspase-9, and induction of activated caspase-3. In the brainstems of ts1-infected mice, activated caspase-3 and damaged mitochondria were identified in astrocytes within areas showing spongiform degeneration. Together the data imply that both ER stress- and mitochondrial stress-related apoptotic pathways are involved in ts1-induced astrocyte death.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalJournal of neurovirology
Volume10
Issue number3
DOIs
StatePublished - Jun 2004

Keywords

  • Apoptosis
  • Astrocyte
  • Caspase
  • ER stress
  • Mitochondrial stress
  • MoMuLV-ts1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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