Ferritin and the response to oxidative stress
Ferritin and the response to oxidative stress
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DOI：
10.1042/0264-6021:3570241
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发表时间：
2001-07-01
影响因子：
4.1
通讯作者：
Torti, FM
中科院分区：
文献类型：
--
作者：
Orino, K;Lehman, L;Torti, FM
铁是正常细胞生长和增殖所必需的。然而，过量的铁是潜在有害的，因为它可以通过芬顿化学催化有毒活性氧物质（ROS）的形成。由于这个原因，细胞已经进化出高度调节的机制来控制细胞内的铁水平。其中最主要的是铁蛋白中的铁螯合作用。铁蛋白是一种24个亚基的蛋白质，由两种亚基类型组成，称为H和L。铁蛋白H亚基具有催化二价铁氧化的强效铁氧化酶活性，而铁蛋白L在铁成核和蛋白质稳定性中起作用。在本研究中，我们报告说，增加合成的两个亚基的铁蛋白发生在HeLa细胞暴露于氧化应激。还观察到响应于氧化应激的铁响应元件结合蛋白的活性增加。然而，这种激活是短暂的，允许铁蛋白蛋白诱导随后进行。为了评估铁蛋白诱导是否减少ROS的积累，并测试铁蛋白H和L亚基在此过程中的相对贡献，我们制备了稳定的转染子，其在四环素响应启动子的控制下过表达铁蛋白H或铁蛋白L cDNA。我们观察到，无论是铁蛋白H或铁蛋白L的过度表达减少了响应氧化剂挑战的ROS的积累。
Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reactive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron levels. Chief among these is the sequestration of iron in ferritin. Ferritin is a 24 subunit protein composed of two subunit types, termed H and L. The ferritin H subunit has a potent ferroxidase activity that catalyses the oxidation of ferrous iron, whereas ferritin L plays a role in iron nucleation and protein stability. In the present study we report that increased synthesis of both subunits of ferritin occurs in HeLa cells exposed to oxidative stress. An increase in the activity of iron responsive element binding proteins in response to oxidative stress was also observed. However, this activation was transient, allowing ferritin protein induction to subsequently proceed. To assess whether ferritin induction reduced the accumulation of ROS, and to test the relative contribution of ferritin H and L subunits in this process, we prepared stable transfectants that overexpressed either ferritin H or ferritin L cDNA under control of a tetracycline-responsive promoter. We observed that overexpression of either ferritin H or ferritin L reduced the accumulation of ROS in response to oxidant challenge.