GADD45 is an oxidative stress response protein.
Bower-JJ; Leonard-SS; Qian-Y; Chen-F; Shi-X
FASEB J 2003 Mar; 17(5)(Part 2):A977-A978
Cell cycle arrest is a major mechanism for the reparation of DNA damage caused by a variety of insults including UV-induced damage, radiation, and exposure to some transition metals. GADD45 (growth arrest and DNA damage-inducible protein 45) is one of many proteins involved in the regulation of cell cycle arrest. This protein has been shown to interfere with the interaction between the cyclin dependent kinase, cdc2, and Cyclin B1, causing cell cycle arrest at the G2/M phase. In this report we investigated the involvement of reactive oxygen species (ROS) in Cr(VI)- and As(III)-induced GADD45 expression in the human airway epithelial cell line, BEAS2B. Cr(VI) induces ROS generation as demonstrated by ESR and confocal microscopy using specific fluorescent dyes for superoxide (O2) and H2O2, the precursor of hydroxyl radical (OH). Western blots indicated an induction of GADD45 by Cr(VI) and As(III), which is correlated with the generation of ROS. Here we report that GADD45 is induced in response to ROS generation, particularly O2- and OH. Furthermore, the induction of GADD45 by Cr(VI) was suppressed by the over-expression of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Since the overexpression of SOD and GPx substantially decreased GADD45 induction by Cr(VI), we concluded that GADD45 is an oxidative stress response protein.
Cellular-function; Cell-function; Cellular-structures; DNA-damage; Ultraviolet-radiation; Radiation; Transition-metals; Proteins; Stress
Abstract; Conference/Symposia Proceedings
The FASEB Journal, Experimental Biology 2003, San Diego, California, April 11-15, 2003