标题：Lithium promotes the production of reactive oxygen species via GSK-3Β/TSC2/TOR signaling in the gill of zebrafish (Danio rerio)
作者：Liu, Dongwu ;Gao, Lili ;Zhang, Zhuangzhuang ;Tao, Shiyi ;Pang, Qiuxiang ;Li, Ao ;Deng, Hongkuan ;Yu, Hairui
作者机构：[Liu, Dongwu ;Gao, Lili ;Zhang, Zhuangzhuang ;Tao, Shiyi ;Pang, Qiuxiang ;Li, Ao ;Deng, Hongkuan ] Laboratory of Developmental and Evolutionary Biolog 更多
摘要：In this study, the mechanism that lithium (Li) promotes the production of reactive oxygen species (ROS) via the glycogen synthase kinase-3β (GSK-3β)/tuberous sclerosis complex 2 (TSC2)/target of rapamycin (TOR) signaling was investigated in the gill of zebrafish (Danio rerio). After the zebrafish were treated by 25 and 50 mg/L Li+, the mRNA expression of GSK-3β and TSC2 was inhibited, but the expression of TOR was induced in the gill of zebrafish. The levels of hydrogen peroxide (H2O2), superoxide anion (O2·-), and hydroxy radical (·OH) as well as the activity of superoxide dismutase (SOD) were increased, while the activities of catalase (CAT), glutathione peroxidase (GSH-PX), and peroxidase (POD) were decreased by 25 and 50 mg/L Li+treatments. In the ZF4 cells, the mRNA expression of GSK-3β and TSC2 was inhibited, but TOR expression was induced by 1, 5, and 10 mmol/L Li+treatments. To further confirm that lithium promoted ROS production via GSK-3β inhibition, GSK-3β RNA was interfered. It was found that the interference of GSK-3β RNA induced the TSC2/TOR signaling. The levels of H2O2, O2·-, and ·OH were increased, but the activities of CAT, GSH-PX, and POD were decreased by GSK-3β RNA interference. In addition, lithium decreased the mitochondrial membrane potential (MMP) with Rhodamine-123 assay, but increased the levels of ROS by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) assay. The present results indicated that lithium promoted the ROS production through the GSK-3β/TSC2/TOR signaling in the gill of zebrafish.
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