TY - JOUR
T1 - Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected astrocytes
AU - Liu, Na
AU - Scofield, Virginia L.
AU - Qiang, Wenan
AU - Yan, Mingshan
AU - Kuang, Xianghong
AU - Wong, Paul K.Y.
N1 - Funding Information:
We are grateful to Dr. Xiaodong Wang for providing tBid antibody. Drs. Gordon C. Shore and Mary Sutherland provided the P20HA and rtTA adenovirus vectors and anti-BAP31 antibody, and Drs. Dhyan Chandra and Dean Tang provided valuable suggestions. We also thank Cynthia Kim, Shawna Johnson, and Chistine K. Brown for their assistance in preparing the manuscript, and Shoufeng Wang, Dr. Yuhong Jiang, and Lifang Zhang for their technical support. This work was supported by NIH grants MH071583 and NS43984, Center Grant ES07784, and Core Grant CA 16672.
PY - 2006/5/10
Y1 - 2006/5/10
N2 - 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.
AB - 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.
KW - Apoptotic pathways
KW - Astrocytes
KW - BAP20
KW - Caspase 8
KW - DR5
KW - Endoplasmic reticulum stress
KW - GADD153/CHOP
KW - Retrovirus
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U2 - 10.1016/j.virol.2006.01.002
DO - 10.1016/j.virol.2006.01.002
M3 - Article
C2 - 16466764
AN - SCOPUS:33646234686
VL - 348
SP - 398
EP - 405
JO - Virology
JF - Virology
SN - 0042-6822
IS - 2
ER -