Abstract
Melanogenesis in melanocytes is considered one of the dermal reactions against ultraviolet (UV) rays. The melanogenesis in melanocytes is induced by cytokines, which are discharged from keratinocytes that exist in the intercellular space around the melanocyte, as a result of UV irradiation. However, the mechanism of self-induced melanogenesis in a single melanocyte, or co-induced melanogenesis between multiple melanocytes, has not been fully explained. We conducted a verification study evaluating the bystander effect, in an attempt to elucidate the mechanism of the co-induced melanogenesis by multiple melanocytes.
We successfully identified the bystander effect indicated by the melanogenesis, as a result of medium transfer of B16 melanoma cells, which were cultured for 24 hours after being exposed to UVA irradiation, to non-irradiated cells (bystander cells). Through our confirmation study regarding the functional mechanism of bystander cells, we found reduced level of mitochondrial membrane potential after 1-3 hours from the medium transfer, increased level of intracellular oxidation after 12 hours, and the generation of melanin radicals, as well as delayed long-lived radicals after 24 hours from the medium transfer. Further study on bystander factors revealed that the administration of EGTA treatment at the time of medium transfer leads to inhibition of melanogenesis, and neutralization of mitochondrial membrane potential level, as well as the intracellular oxidation level to the control level. The results showed that the UVA irradiation bystander effect in the B16 mouse melanoma cells, indicated by melanogenesis, was induced by the increase of intracellular oxidation level, as a result of calcium ions, one of the bystander factors, acting on mitochondria.
