Ferritin and the response to oxidative stress

被引:399
作者
Orino, K
Lehman, L
Tsuji, Y
Ayaki, H
Torti, SV [1 ]
Torti, FM
机构
[1] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA
[2] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA
[3] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA
[4] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27157 USA
关键词
hydrogen peroxide; iron; iron storage proteins; reactive oxygen species; transfection;
D O I
10.1042/0264-6021:3570241
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:241 / 247
页数:7
相关论文
共 44 条
[41]  
TSUJI Y, 1993, J BIOL CHEM, V268, P7270
[42]  
VILE GF, 1993, J BIOL CHEM, V268, P14678
[43]   Functional antioxidant responsive elements [J].
Wasserman, WW ;
Fahl, WE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5361-5366
[44]   OXIDATION PATHWAYS FOR THE INTRACELLULAR PROBE 2',7'-DICHLOROFLUORESCIN [J].
ZHU, H ;
BANNENBERG, GL ;
MOLDEUS, P ;
SHERTZER, HG .
ARCHIVES OF TOXICOLOGY, 1994, 68 (09) :582-587