Possible involvement of both endoplasmic reticulum- and mitochondria-dependent pathways in MoMuLV-ts1-induced apoptosis in astrocytes.
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 gPr80(env). 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 eIF2 alpha, 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.
Liu
Na
N
Department of Carcinogenesis, University of Texas, MD Anderson Cancer Center, Science Park-Research Division, Smithville, 78957, USA.
Kuang
Xianghong
X
Kim
Hun-Taek
HT
Stoica
George
G
Qiang
Wenan
W
Scofield
Virginia Lee
VL
Wong
Paul K Y
PK
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000821:virology*; D015153:Blotting, Western; D001933:Brain Stem / Q000473:pathology / Q000648:ultrastructure / Q000821:virology; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000648:ultrastructure / Q000821:virology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure / Q000821:virology*; D008979:Moloney murine leukemia virus / Q000502:physiology; D012192:Retroviridae Infections / Q000473:pathology / Q000503:physiopathology*; D014412:Tumor Virus Infections / Q000473:pathology / Q000503:physiopathology*