A 50-Hz magnetic-field exposure promotes human amniotic cells proliferation via SphK-S1P-S1PR cascade mediated ERK signaling pathway

Extremely low-frequency electromagnetic fields (ELF-EMFs) present a kind of common non-ionizing radiation in public and occupational environments. Previous studies have suggested that ELF-EMF exposure might have a potential impact on co-carcinogenesis and the progression of tumorigenesis by inducing cell proliferation. However, the underlying mechanisms remain largely unknown. In this study, we investigated the possible role of the sphingosine-l-phosphate (S1P)-related pathway in regulating cell proliferation induced by 50-Hz, 0.4-mT magnetic-field (MF) exposure. The results showed that MF exposure significantly promoted sphingosine kinase 1 (SphK1) activity, and that inhibition of the SphK1-S1P-S1P receptor (S1PR) pathway could remarkably reverse MF-induced cell proliferation. Additionally, we could infer indirectly from an exogenous-S1P experiment that MF-induced S1P might act on S1PR1/3 in a paracrine and/or autocrine manner to mediate the proliferation effect. Notably, although the MF activated the extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways, the SphK1-S1P-S1PR1/3 cascade regulated MF-induced proliferation by activating the ERK rather than the Akt pathway. Taken together, the findings of this study indicated that the SphK1-S1P-S1PR1/3 cascade played an important role in MF-induced proliferation by mediating the ERK signaling pathway, which could bring new insights into understanding and preventing the adverse effects of MFs.