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Protective effect of Drosophila glutathione transferase omega 1 against hydrogen peroxide-induced neuronal toxicity

Lee, So Yeon, Lim, In-Ae, Kang, Ga-Un, Cha, Sun-Joo, Altanbyek, Volodya, Kim, Hyung-Jun, Lee, Seongsoo, Kim, Kiyoung, Yim, Jeongbin
Gene 2015 v.568 pp. 203-210
Drosophila, adults, glutathione transferase, hydrogen peroxide, loss-of-function mutation, mitogen-activated protein kinase, models, mutants, neurons, oxidative stress, protective effect, sequence analysis, toxicity
Glutathione transferase omega (GSTO) belongs to a recently identified family of glutathione transferase (GST) and presents several known functions. In Drosophila, despite the high sequence identity among the four GstO isoforms, they present different physiological functions. Herein, we showed that GstO1, which is one of the Drosophila GstOs, is highly expressed in adult heads. We determined the three-dimensional structure of GstO1, by homology modeling. Furthermore, we show that GstO1 loss-of-function mutant flies display reduced survival than the control flies when subjected to H2O2 treatment. Interestingly, the neuronal-specific expression of GstO1 in a GstO1 loss-of-function mutant background rescued H2O2-induced toxicity. We further showed that GstO1 inhibits H2O2-mediated activation of the mitogen-activated protein kinase (MAPK) pathway. Collectively, our findings provide valuable new insights into the tissue-specific protective mechanisms of Drosophila GstOs during oxidative stress.