Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens
Avian reovirus S1133-induced DNA damage signaling and subsequent apoptosis in cultured cells and in chickens
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DOI：
10.1007/s00705-011-1063-3
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发表时间：
2011-11-01
影响因子：
2.7
通讯作者：
Shih, Wen-Ling
中科院分区：
文献类型：
--
作者：
Lin, Ping-Yuan;Liu, Hung-Jen;Shih, Wen-Ling
在本研究中，研究了 ARV S1133 介导的细胞凋亡中的细胞内信号传导。使用微阵列检查抗逆转录病毒S1133感染后细胞的基因表达谱和抗逆转录病毒编码的促凋亡蛋白σ C过表达。分析表明，在一组 DNA 损伤响应基因中，DDIT-3 和 GADD45 α 均因病毒感染和 sigma C 过度表达而上调。进一步的研究表明，两种治疗都会引起 DNA 断裂，从而增加 DNA 损伤反应蛋白的表达和/或磷酸化。 ROS 和脂质过氧化水平增加，ARV S1133 和 sigma C 引起 DNA 损伤信号介导的细胞凋亡。 ROS 清除剂 NAC、咖啡因和 ATM 特异性抑制剂显着降低 ARV S1133 和 sigma C 诱导的 DNA 断裂、DDIT-3 和 GADD45 α 表达、H2AX 磷酸化和细胞凋亡。 DDIT-3 和 GADD45 α 的过表达增强了 ARV S1133 和 sigma C 诱导的氧化应激和细胞凋亡。总之，我们的结果证明 DNA 损伤信号通路参与了 ARV S1133 和 sigma C 诱导的细胞凋亡。
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.