背景:Sirtuin7(SIRT7)在多种疾病进展中至关重要。重要的是,SIRT7与黑色素产生有关。然而,SIRT7是否调节白癜风尚不清楚。因此,我们旨在研究SIRT7对色素沉着和葡萄糖6-磷酸脱氢酶(G6PD)修饰的影响。
方法:在击倒SIRT7和G6PD之后,使用商业试剂盒评估黑素细胞的色素沉着,免疫荧光,和蛋白质印迹分析。使用免疫共沉淀分析SIRT7介导的G6PD的琥珀酰化,免疫荧光,蛋白质印迹分析,和环己酰亚胺追踪实验。
结果:我们发现SIRT7在白癜风皮损中高表达。SIRT7的敲低增加酪氨酸酶活性,黑色素含量,和α-黑素细胞刺激激素的水平,MITF,TYR,TRP1和TRP2。此外,SIRT7直接与G6PD相互作用。沉默的SIRT7促进了G6PD的琥珀酰化并增强了其蛋白稳定性。G6PD敲低逆转了SIRT7表达降低对黑色素产生的影响。
■SIRT7的沉默通过琥珀酰化G6PD促进黑素细胞的色素沉着,提示SIRT7介导的G6PD去琥珀酰化可能促进白癜风的进展。
BACKGROUND: Sirtuin 7 (
SIRT7) is pivotal in diverse diseases progression. Importantly,
SIRT7 is associated with melanin production. However, whether
SIRT7 regulates vitiligo is unclear. Therefore, we aimed to investigate the effects of SIRT7 on pigmentation and the modification of glucose 6-phosphate dehydrogenase (G6PD).
METHODS: After knockdown SIRT7 and G6PD, pigmentation of melanocytes was evaluated using commercial kits, immunofluorescence, and Western blot analysis. The succinylation of G6PD mediated by SIRT7 was analyzed using co-immunoprecipitation, immunofluorescence, Western blot analysis, and cycloheximide-chase experiment.
RESULTS: We found that SIRT7 was highly expressed in vitiligo skin lesions. Knockdown of SIRT7 increased tyrosinase activity, melanin content, and the levels of α-melanocyte-stimulating hormone, MITF, TYR, TRP1, and TRP2. Additionally,
SIRT7 directly interacted with G6PD. Silenced SIRT7 promoted the succinylation of G6PD and enhanced its protein stability. G6PD knockdown reversed the effect of reduced
SIRT7 expression on melanin production.
UNASSIGNED: Silencing of SIRT7 promotes pigmentation of melanocytes by succinylating G6PD, suggesting that SIRT7-mediated G6PD desuccinylation may promote vitiligo progression.