Research articleMelatonin exerts protective effect on N2a cells under hypoxia conditions through Zip1/ERK pathway

- Melatonin can decrease the activity of caspase-3, -8, and -9 in hypoxia N2a cells.
- Melatonin markedly activated Bcl-2 and decreased Bax expression.
- Melatonin can increase SOD, and decrease MDA and ROS in hypoxia N2a cells.
- Melatonin induces Zn2+ influx via Zip1 in hypoxia N2a cells.
- Melatonin upregulated pERK1/2 and pERK5 via Zip1 in hypoxia N2a cells.

Melatonin plays a neuroprotective role in different CNS injuries. However, the molecular mechanisms underlying neuroprotection by melatonin are not well understood. Here, we studied the effects of melatonin in hypoxia-induced N2a cells and our results demonstrated that melatonin not only reduced the level of ROS and MDA, induced the increase of SOD, but also increased the cell proliferation and inhibited cell apoptosis in hypoxia-induced N2a cells. Moreover, we identified that melatonin can activate the MAPK/ERK pathway via upregulating the expression of Zip1. Therefore, this study provides a new mechanism of melatonin and need our further study in detail.