DHA ameliorates MeHg‑induced PC12 cell apoptosis by inhibiting the ROS/JNK signaling pathway

Zhang,Hong; Wang,Susu; Wang,Yaqian; Lu,Anxin; Hu,Chunping; Yan,Chonghuai

doi:10.3892/mmr.2021.12197

DHA ameliorates MeHg‑induced PC12 cell apoptosis by inhibiting the ROS/JNK signaling pathway

Authors:
- Hong Zhang
- Susu Wang
- Yaqian Wang
- Anxin Lu
- Chunping Hu
- Chonghuai Yan
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Affiliations: Ministry of Education‑Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China, School of Public Health, Shanghai Jiao Tong University, Shanghai 200025, P.R. China
Published online on: June 3, 2021 https://doi.org/10.3892/mmr.2021.12197
Article Number: 558
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent studies have reported that methylmercury (MeHg) induces neuronal apoptosis, which is accompanied by abnormal neurological development. Despite the important role of docosahexaenoic acid (DHA) in maintaining the structure and function of the brain, as well as improving neuronal apoptosis induced by MeHg, the exact mechanism remains unknown. The present study hypothesized that the reactive oxygen species (ROS)‑mediated JNK signaling pathway may be associated with the protective effect of DHA against MeHg‑induced PC12 cell apoptosis. Cell Counting Kit‑8, TUNEL staining, flow cytometry, ROS detection, PCR and western blot analysis were performed. The results demonstrated that MeHg inhibited the activity of PC12 cells, causing oxidative damage and promoting apoptosis; however, DHA significantly attenuated this effect. Mechanistic studies revealed that MeHg increased intracellular ROS levels and JNK protein phosphorylation, and decreased the expression levels of the anti‑apoptotic protein Bcl‑2, whereas DHA reduced ROS levels and JNK phosphorylation, and increased Bcl‑2 expression. In addition, the ROS inhibitor N‑acetyl‑l‑cysteine (NAC) was used to verify the experimental results. After pretreatment with NAC, expression levels of Bcl‑2, Bax, phosphorylated‑JNK and JNK were assessed. Bcl‑2 protein expression was increased and the Bcl‑2/Bax ratio was increased. Moreover, the high expression levels of phosphorylated‑JNK induced by MeHg were significantly decreased. Based on the aforementioned results, the present study indicated that the effects of DHA against MeHg‑induced PC12 cell apoptosis may be mediated via the ROS/JNK signaling pathway.

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