aquatic birnavirus-induced er stress-mediated death signaling contribute to downregulation of bcl-2 family proteins in salmon embryo cells水生birnavirus-induced er stress-mediated死亡信号的差别有助于对这些基因bcl - 2家族在大马哈鱼胚胎细胞蛋白质.pdf

Aquatic Birnavirus-Induced ER Stress-Mediated Death Signaling Contribute to Downregulation of Bcl-2 Family Proteins in Salmon Embryo Cells 1 2 3 1 Hui Ling Huang , Jen Leih Wu , Mark Hung Chih Chen *, Jiann Ruey Hong * 1 Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan, 2 Laboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan, 3 Bioluminescence in Life-image Laboratory, Institute of Biotechnology, Department of Biotechnology, Hungkuang University, Taichung, Taiwan Abstract Aquatic birnavirus induces mitochondria-mediated cell death, but whether connects to endoplasmic reticulum (ER) stress is still unknown. In this present, we characterized that IPNV infection triggers ER stress-mediated cell death via PKR/eIF2a phosphorylation signaling for regulating the Bcl-2 family protein expression in fish cells. The IPNV infection can induce ER stress as follows: (1) ER stress sensor ATF6 cleavaged; (2) ER stress marker GRP78 upregulation, and (3) PERK/ eIF2aphosphorylation. Then, the IPNV-induced ER stress signals can induce the CHOP expression at early (6 h p.i.) and middle replication (12 h p.i.) stages. Moreover, IPNV-induced CHOP upregulation dramatically correlates to apparently downregulate the Bcl-2 family proteins, Bcl-2, Mcl-1 and Bcl-xL at middle replication stage (12 h p.i.) and produces mitochondria membrane potential (MMP) loss and cell death. Furthermore, with GRP78 synthesis inhibitor momitoxin (VT) and PKR inhibitor 2-aminopurine (2-AP) treatment for blocking GRP78 expression and eIF