SIRT7介导的G6PD脱琥珀酰化促进白癜风病情发展的机制

IF 3.1 4区 医学 Q3 IMMUNOLOGY
Yiyun Yang, Haidong Long, Lan Long, Bin Guo
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引用次数: 0

摘要

背景:Sirtuin 7(SIRT7)在多种疾病的进展中起着关键作用。重要的是,SIRT7 与黑色素的生成有关。然而,SIRT7 是否调控白癜风尚不清楚。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:在敲除 SIRT7 和 G6PD 后,使用商业试剂盒、免疫荧光和 Western 印迹分析评估黑色素细胞的色素沉着。使用共免疫共沉淀、免疫荧光、Western 印迹分析和环己亚胺酶实验分析了 SIRT7 介导的 G6PD 的琥珀酰化:结果:我们发现SIRT7在白癜风皮损中高表达。结果:我们发现SIRT7在白癜风皮损中高表达,敲除SIRT7可提高酪氨酸酶活性、黑色素含量以及α-黑色素细胞刺激素、MITF、TYR、TRP1和TRP2的水平。此外,SIRT7 与 G6PD 直接相互作用。沉默的 SIRT7 促进了 G6PD 的琥珀酰化,并增强了其蛋白质的稳定性。G6PD 敲除逆转了 SIRT7 表达减少对黑色素生成的影响:沉默SIRT7可通过琥珀酰化G6PD促进黑色素细胞的色素沉着,这表明SIRT7介导的G6PD脱琥珀酰化可能会促进白癜风的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Mechanism of desuccinylation of G6PD mediated by SIRT7 to promote vitiligo disease progression

Mechanism of desuccinylation of G6PD mediated by SIRT7 to promote vitiligo disease progression

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.

Conclsuion

Silencing of SIRT7 promotes pigmentation of melanocytes by succinylating G6PD, suggesting that SIRT7-mediated G6PD desuccinylation may promote vitiligo progression.

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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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