A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway

Li,Dongjie; Wei,Yutao; Xu,Shangzhi; Niu,Qiang; Zhang,Mei; Li,Shugang; Jing,Mingxia

doi:10.3892/mmr.2018.8383

A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway

Authors:
- Dongjie Li
- Yutao Wei
- Shangzhi Xu
- Qiang Niu
- Mei Zhang
- Shugang Li
- Mingxia Jing
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Affiliations: Department of Public Health, School of Medicine, Shihezi University, Shihezi, Xinjiang 832002, P.R. China, Department of Cardiothoracic Surgery, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang 832000, P.R. China
Published online on: January 5, 2018 https://doi.org/10.3892/mmr.2018.8383
Pages: 4422-4432
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic‑induced apoptosis. Due to a few controversial issues about arsenic‑mediated extracellular signal‑regulated MAP kinases (ERK) signaling, a meta‑analysis was performed. Subgroup analyses demonstrated that high doses (≥2 µmol/l) of arsenic increased the expression of Ras, ERK, ERK1, ERK2, phosphorylated (p)‑ERK, p‑ERK1, and p‑ERK2, while low doses (<2 µmol/l) decreased the expression of Ras, ERK1, p‑ERK, and p‑ERK2 when compared to control groups. Long term exposure (>24 h) to arsenic led to inhibition of expression of ERK1, p‑ERK1, and p‑ERK2, whereas short‑term exposure (≤24 h) triggered the expression of ERK1, ERK2, p‑ERK, p‑ERK1, and p‑ERK2. Furthermore, normal cells exposed to arsenic exhibited higher production levels of Ras and p‑ERK. Conversely, exposure of cancer cells to arsenic showed a lower level of production of Ras and p‑ERK as well as higher level of p‑ERK1 and p‑ERK2 as compared to control group. Short‑term exposure of normal cells to high doses of arsenic may promote ERK signaling pathway. In contrast, long‑term exposure of cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This study may be helpful in providing a theoretical basis for the diverging result of arsenic adverse effects on one hand and therapeutic mechanisms on the other concerning arsenic‑induced apoptosis.

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