Protective mechanism of morin against ultraviolet B-induced cellular senescence in human keratinocyte stem cells.

OBJECTIVE

Ultraviolet-B (UVB) irradiation is a major inducer of DNA damage in the epidermis. Here we investigated the protective mechanism of polyphenolic phytonutrient, morin against UVB-induced DNA damage in human keratinocyte stem cells (KSC).

CONCLUSIONS

After confirming the characteristics of the KSC, we examined the protective ability of morin against the cell damage of KSC under UVB irradiation condition. As a result, morin significantly inhibited the UVB-induced damage to KSC. These inhibitory effects by morin were also confirmed by the senescence-associated beta-galactosidase and alkaline comet assays. Next, we monitored the effects of morin on the UVB-induced production of inflammatory cytokines. Morin significantly decreased the production of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the UVB-irradiated KSC. Also, morin significantly inhibited the UVB-induced phosphorylation of ataxia telangiectasia mutated (ATM), serine threonine kinase checkpoint kinase 2, tumor suppressor protein 53 (p53), c-Jun N-terminal kinase/stress-activated protein kinase, p38/mitogen-activated protein kinase, S6 ribosomal protein, and histone 2A family member X in KSC. Furthermore, while UVB irradiation induced p53 reporter activation in KSC, morin significantly inhibited UVB-induced p53 reporter activation in KSC. In addition, mouse double minute 2 homolog (MDM2, p53 E3 ubiquitin protein ligase) inhibitor significantly increased the p53 reporter activation in the UVB-irradiated KSC, but morin decreased the MDM2 inhibitor-mediated increase in p53 reporter activation. On the contrary, ATM inhibitor did not affect the protective effect of morin in UVB irradiation-induced p53 reporter activation. Collectively, these findings suggest that morin could effectively enrich the p53 specific ligasing ability of MDM2 in UVB irradiation-induced p53 activation.