Dual roles of γ-glutamyl transpeptidase in the cellular response to reactive oxygen species

CHED 821

Stacy Crum, tfrielle@ship.edu and Thomas Frielle, tfrielle@ship.edu. Department of Chemistry, Shippensburg University, 1871 Old Main Drive, Shippensburg, PA 17257
Glutathione, the most abundant no-protein thiol is responsible for reducing ROS and preventing subsequent cellular damage. Renal γ-glutamyl transpeptidase (γGT) plays a vital role in the glutathione (GSH)-dependent cellular response to ROS. γGT maintains the cellular concentration of GSH by initiating the Gamma Glutamyl Cycle allowing for the re-uptake and re-synthesis of GSH. Paradoxically, the action of γGT has recently been reported to directly increase the production of ROS, thus amplifying the cellular stress response. Preliminary evidence suggests that the product of γGT activity, cysteinylglycine more readily reduces Fe+3 than does GSH. The resulting Fe+2 is then able to reduce molecular oxygen, which then is able to react with water to form hydrogen peroxide, a potent ROS. In this study, the role of γGT in protecting cellular components and its opposing role in increasing the concentration of ROS will be investigated to evaluate the contributions of each.