Department of Dermatology, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (Longgang Maternity and Child Institute of Shantou University Medical College), Shenzhen, China.
Immun Inflamm Dis. 2024 Aug;12(8):e1341. doi: 10.1002/iid3.1341.
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).
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.
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.
Silencing of SIRT7 promotes pigmentation of melanocytes by succinylating G6PD, suggesting that SIRT7-mediated G6PD desuccinylation may promote vitiligo progression.
Sirtuin 7（SIRT7）在多种疾病的进展中起着关键作用。重要的是，SIRT7 与黑色素的产生有关。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。
敲低 SIRT7 和 G6PD 后，使用商业试剂盒、免疫荧光和 Western blot 分析评估黑素细胞的色素沉着。使用共免疫沉淀、免疫荧光、Western blot 分析和环己酰亚胺追踪实验分析 SIRT7 介导的 G6PD 琥珀酰化。
我们发现 SIRT7 在白癜风皮损中高表达。敲低 SIRT7 增加了酪氨酸酶活性、黑色素含量以及 α-促黑素细胞激素、MITF、TYR、TRP1 和 TRP2 的水平。此外，SIRT7 与 G6PD 直接相互作用。沉默 SIRT7 促进了 G6PD 的琥珀酰化，增强了其蛋白质稳定性。G6PD 敲低逆转了 SIRT7 表达减少对黑色素生成的影响。
沉默 SIRT7 通过琥珀酰化 G6PD 促进黑素细胞的色素沉着，表明 SIRT7 介导的 G6PD 去琥珀酰化可能促进白癜风的进展。
