Orexin-A protects SH-SY5Y cells against H(2)O(2)-induced oxidative damage via the PI3K/MEK(1/2)/ERK(1/2) signaling pathway

Orexin-A elicits multiple potent effects on a variety of tumor cells via different signaling pathways. However, it is unknown whether it has a neuroprotective effect on SH-SY5Y human neuroblastoma cells. This study investigated the neuroprotective effect of Orexin-A against hydrogen peroxide (H(2)O(2))-induced oxidative damage in SH-SY5Y cells and the underlying mechanism. H(2)O(2) treatment decreased the viability of SH-SY5Y cells, induced apoptosis, and decreased superoxide dismutase activity. Orexin-A attenuated these effects, indicating that it protects SH-SY5Y cells against H(2)O(2)-induced oxidative damage. Pre-treatment with Orexin-A also attenuated H(2)O(2)-induced increases in phosphorylation of MEK(1/2) and ERK(1/2). Moreover, these effects of Orexin-A were reduced in the presence of the PI3K inhibitor LY294002. Finally, pre-treatment with LY294002 abrogated attenuation of the H(2)O(2)-induced decrease in cell viability and increase in caspase-3/7 activity by Orexin-A. These results show that the PI3K/MEK(1/2)/ERK(1/2) signaling pathway is involved in the neuroprotective effects of Orexin-A against H(2)O(2)-induced oxidative damage in SH-SY5Y cells. Our findings provide insight into the neuroprotective effects of Orexin-A and the underlying mechanism, which will be useful for the treatment of nervous system diseases.