Department of Dermatology, Dongguk University Ilsan Hospital, 410-773 Goyang-si, Gyenggi-do, Korea.
Acta Derm Venereol. 2020 Apr 6;100(8):adv00109. doi: 10.2340/00015555-3473.
DNA damage and oxidative stress play a critical role in photoageing. Seborrhoeic keratosis (SK) affects sunlight-exposed sites in aged individuals. This study examined the mechanism of photoageing in SK. The guanine deaminase gene, which is involved in purine metabolism, was upregulated with uric acid levels and p21 in SK. Guanine deaminase was detectable in keratinocytes. Repeated exposure to ultraviolet (UV) increased levels of guanine deaminase, together with DNA damage, such as γ-H2AX and cyclobutane pyrimidine dimer formation, generation of reactive oxygen species, and keratinocyte senescence, which were reversed by guanine deaminase knockdown. However, guanine deaminase overexpression and H2O2 formed γ-H2AX, but not cyclobutane pyrimidine dimer. Loss-of-function guanine deaminase mutants reduced the metabolic end-product uric acid, which was increased by exposure to exogenous xanthine. Repeated exposure to UV increased levels of uric acid. Exogenous uric acid increased cellular senescence, reactive oxygen species, and γ-H2AX, similar to guanine deaminase. Overall, guanine deaminase upregulation increased UV-induced keratinocyte senescence in SK, via uric acid mediated by reactive oxygen species followed by DNA damage.
DNA 损伤和氧化应激在光老化中起着关键作用。脂溢性角化病（SK）影响老年人暴露于阳光的部位。本研究探讨了 SK 中光老化的机制。鸟嘌呤脱氨酶基因参与嘌呤代谢，其水平随尿酸和 SK 中的 p21 而上调。角质形成细胞中可检测到鸟嘌呤脱氨酶。反复暴露于紫外线（UV）会增加鸟嘌呤脱氨酶的水平，同时还会导致 DNA 损伤，如 γ-H2AX 和环丁烷嘧啶二聚体形成、活性氧的产生以及角质形成细胞衰老，这些都可以通过敲低鸟嘌呤脱氨酶来逆转。然而，鸟嘌呤脱氨酶过表达和 H2O2 形成 γ-H2AX，但不形成环丁烷嘧啶二聚体。失活的鸟嘌呤脱氨酶突变体减少了代谢终产物尿酸，而外源性黄嘌呤的暴露会增加尿酸的产生。反复暴露于 UV 会增加尿酸的水平。外源性尿酸会增加细胞衰老、活性氧和 γ-H2AX，这与鸟嘌呤脱氨酶相似。总的来说，鸟嘌呤脱氨酶的上调通过活性氧介导的尿酸增加，随后是 DNA 损伤，增加了 SK 中 UV 诱导的角质形成细胞衰老。
