Protective mechanism of morin against ultraviolet B-induced cellular senescence in human keratinocyte stem cells. (January 2014)

• Record Type: Journal Article
• Authors: Lee, Jienny; Shin, Yeun-Kyung; Song, Jae-Young; Lee, Kyung-Woo
• Is Part Of: International journal of radiation biology. Volume 90:Number 1(2014:Jan.)
• Page Start: 20
• Page End: 28
• Publication Date: 2014-01
• Subjects: Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.3109/09553002.2013.835502
• Languages: English
• ISSNs: 0955-3002

Abstract

<abstract> <title>Abstract</title> <p> <italic>Purpose</italic>: 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).</p> <p> <italic>Results and conclusions</italic>: 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.</p> </abstract>