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|標題:||Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens|
|期刊/報告no：:||Archives of Virology, Volume 156, Issue 11, Page(s) 1917-1929.|
|摘要:||In this study, intracellular signaling in ARV S1133-mediated apoptosis was investigated. A microarray was used to examine the gene expression profiles of cells upon ARV S1133 infection and ARV-encoded pro-apoptotic protein sigma C overexpression. The analysis indicated that in the set of DNA-damage-responsive genes, DDIT-3 and GADD45 alpha were both upregulated by viral infection and sigma C overexpression. Further investigation demonstrated that both treatments caused DNA breaks, which increased the expression and/or phosphorylation of DNA damage response proteins. ROS and lipid peroxidation levels were increased, and ARV S1133 and sigma C caused apoptosis mediated by DNA damage signaling. ROS scavenger NAC, caffeine and an ATM-specific inhibitor significantly reduced ARV S1133- and sigma C-induced DNA breaks, DDIT-3 and GADD45 alpha expression, H2AX phosphorylation, and apoptosis. Overexpression of DDIT-3 and GADD45 alpha enhanced the oxidative stress and apoptosis induced by ARV S1133 and sigma C. In conclusion, our results demonstrate the involvement of the DNA-damage-signaling pathway in ARV S1133- and sigma C-induced apoptosis.|
|Appears in Collections:||分子生物學研究所|
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