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

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.