Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells
Overexpression of the human ubiquitin E3 ligase CUL4A alleviates hypoxia-reoxygenation injury in pheochromocytoma (PC12) cells
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DOI：
10.1016/j.bbrc.2011.11.054
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发表时间：
2011-12-16
影响因子：
3.1
通讯作者：
Zhang, Jian-Xiang
中科院分区：
文献类型：
--
作者：
Tan, Can;Zhang, Li-Yang;Zhang, Jian-Xiang
泛素 E3 连接酶 CUL4A 在多种细胞过程中发挥着重要作用，包括癌发生和增殖。据报道，缺氧缺血性损伤可诱导CUL4A的表达。然而，CUL4A表达升高对缺氧-复氧损伤的影响目前尚不清楚。本研究利用腺病毒载体介导的基因转移在大鼠嗜铬细胞瘤（PC12）细胞中表达人CUL4A（hCUL4A），并研究hCUL4A表达对缺氧-复氧损伤的影响。在缺氧和复氧的PC12细胞中，我们发现hCUL4A通过调节凋亡相关蛋白和细胞周期调节因子（Bcl-2、caspase-3、p53和p27）来抑制细胞凋亡和DNA损伤；因此，hCUL4A 促进细胞存活。综上所述，我们的结果揭示了 hCUL4A 在 PC12 细胞中对缺氧-复氧损伤的有益作用。 (C) 2011 Elsevier Inc. 保留所有权利。
The ubiquitin E3 ligase CUL4A plays important roles in diverse cellular processes including carcinogenesis and proliferation. It has been reported that the expression of CUL4A can be induced by hypoxic-ischemic injury. However, the effect of elevated expression of CUL4A on hypoxia-reoxygenation injury is currently unclear. In this study, human CUL4A (hCUL4A) was expressed in rat pheochromocytoma (PC12) cells using adenoviral vector-mediated gene transfer, and the effects of hCUL4A expression on hypoxia-reoxygenation injury were investigated. In PC12 cells subjected to hypoxia and reoxygenation, we found that hCUL4A suppresses apoptosis and DNA damage by regulating apoptosis-related proteins and cell cycle regulators (Bcl-2, caspase-3, p53 and p27); consequently, hCUL4A promotes cell survival. Taken together, our results reveal the beneficial effects of hCUL4A in PC12 cells upon hypoxia-reoxygenation injury. (C) 2011 Elsevier Inc. All rights reserved.