부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.virol.2006.01.002 Byline: Na Liu (a), Virginia L. Scofield (a), Wenan Qiang (b), Mingshan Yan (a), Xianghong Kuang (c), Paul K.Y. Wong (a) Keywords: Endoplasmic reticulum stress; Caspase 8; Apoptotic pathways; Astrocytes; DR5; GADD153/CHOP; Retrovirus; BAP20 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 TNF[alpha] 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. Author Affiliation: (a) Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA (b) Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA (c) Department of Pharmacology, School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, PR China Article History: Received 29 August 2005; Revised 23 November 2005; Accepted 4 January 2006