Abstract
BackgroundPrevious studies indicated that cadmium (Cd) increases PI3-kinase/Akt phosphorylation, resulting in an alteration in GSK-3β activity. However, the mechanism of Cd-induced endoplasmic reticulum (ER) stress in neuronal cells has yet to be studied in needs further elucidation. We examined the role of GSK-3β in Cd-induced neuronal cell death and the related downstream signaling pathways.MethodsSH-SY5Y human neuroblastoma cells were treated with 10 or 20 μM BAPTA-AM and 1 μM wortmannin for 30 min and then incubated with 25 μM Cd for 12 h. Apoptotic cells were visualized via DAPI and PI staining. Data were evaluated with one-way analysis of variance (ANOVA) followed by Student’s t-test. Data are expressed as the means ± SD of experiments performed at least three times.ResultsTreatment of human neuronal SH-SY5Y cells with Cd induced ER, stress as evidenced by the increased expression of GRP78, which is a marker of ER stress. Cd exposure significantly increased the phosphorylation of Akt at thr308 and ser473 and that of GSK-3β at ser9 in a time-dependent manner, while the total protein levels of GSK-3β and Akt did not change. Cd-induced apoptosis was higher in GSK-3β-knockdown cells than in normal cells.ConclusionsOur data suggest that Akt/GSK-3β signaling activated by Cd is involved in neuronal cell survival.
Highlights
Cadmium (Cd) is a potent toxic metal that affects various cellular processes, such as cell proliferation and apoptosis
To determine whether Cd induces endoplasmic reticulum (ER) stress in SH-SY5Y cells, we examined the protein expression levels of three ER stress markers, glucose-regulated protein 78 (GRP78), GRP94 and GADD153, after Cd treatment
Cells treated with thapsigargin (TG; 1 μM for 6 ~ 24 h) as a positive control for ER stress showed an increase in the cellular GRP78 protein level after 12 h (Fig. 1)
Summary
Cadmium (Cd) is a potent toxic metal that affects various cellular processes, such as cell proliferation and apoptosis. It can cause DNA damage, reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress [1, 2]. The latter two events are important triggers of the stress response in many cell types [1,2,3]. We found that Cd induces neuronal cell death through ROS production activated by GADD153. We examined the role of GSK-3β in Cd-induced neuronal cell death and the related downstream signaling pathways
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