Böhm Markus, Hill Helene Z
Department of Dermatology, University of Münster, Münster, Germany.
Department of Radiology, Rutgers New Jersey Medical School, Newark, NJ, USA.
F1000Res. 2016 May 12;5:881. doi: 10.12688/f1000research.8582.1. eCollection 2016.
Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA) damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.
α-黑素细胞刺激素（α-MSH）可增加黑色素生成，并保护细胞免受紫外线诱导的DNA损伤。然而，其对线粒体DNA（mtDNA）损伤的影响尚不清楚。我们在一项初步研究中探讨了这个问题，该研究使用了与α-MSH孵育并接受UVB照射的人表皮角质形成细胞和黑素细胞。采用实时降落PCR定量总mtDNA和缺失型mtDNA。检测到的缺失涵盖常见缺失，但对检测更敏感。角质形成细胞中的mtDNA拷贝数比黑素细胞多4.4倍。单独照射不影响拷贝数。在没有UVB的情况下，α-MSH在两种细胞类型中均略微增加了拷贝数，并且随着剂量增加，两种细胞类型中的拷贝数均出现类似的小幅下降。角质形成细胞中缺失型拷贝的频率几乎是黑素细胞中的两倍。α-MSH使角质形成细胞中缺失型拷贝的频率降低了一半，但在黑素细胞中没有作用。UVB剂量依赖性地导致α-MSH处理的黑素细胞中缺失型拷贝数增加。UVB照射对α-MSH处理的角质形成细胞中的缺失型拷贝数影响很小。总之，α-MSH可能通过增加黑色素生成来增强黑素细胞中的mtDNA损伤，而α-MSH对角质形成细胞具有保护作用，在没有照射的情况下保护作用更强。
