White light emitting diode suppresses proliferation and induces apoptosis in hippocampal neuron cells through mitochondrial cytochrome c oxydase-mediated IGF-1 and TNF-α pathways

Abstract

Light emitting diode (LED) light has been tested to treat traumatic brain injury, neural degenerative diseases and psychiatric disorders. Previous studies indicate that blue LED light affects cell proliferation and apoptosis in photosensitive cells and cancer cells. In this study, we demonstrate that white LED light exposure impaired proliferation and induced apoptosis in HeLa and HT-22 hippocampal neural cells, but not C2C12 cells. Furthermore, the mechanisms underlying the effect of white LED light exposure on HT-22 cells were elucidated. In HeLa and HT-22 cells, white LED light activated mitochondrial cytochrome c oxidase (Cco), in association with enhanced ATP synthase activity and elevated intracellular ATP concentration. Also, reactive oxygen species (ROS) and nitric oxide (NO) production were increased, accompanied by higher calcium concentration and lower mitochondrial membrane potential. HT-22 cells exposed to white LED light for 24h showed reduced viability, with higher apoptotic rate and a cell cycle arrest at G0/G1 phase. Concurrently, the mRNA expression and the concentration of IGF-1 were decreased, while that of TNF-α were increased, in light-exposed cells, which was supported by the luciferase activity of both gene promoters. The down-stream mitogen-activated protein kinase (MAPK), AKT/mTOR pathways were inhibited, in association with an activation of apoptotic caspase 3. N-Acetylcysteine, a ROS scavenger, protected the cells from LED light-induced cellular damage, with rescued cell viability and restored mRNA expression of IGF-1 and TNF-α. Our data demonstrate that white LED light suppresses proliferation and induces apoptosis in hippocampal neuron cells through mitochondrial Cco/ROS-mediated IGF-1 and TNF-α pathways.