Spermidine limits diabetes by modulating RIPK1-mediated cell death and inflammation

IF 4 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2024-11-07 DOI:10.1038/s41556-024-01542-4

引用次数: 0

Abstract

We establish a mouse model of progressive diabetes induced by conditional NAT1 deficiency in vascular endothelial cells. NAT1 deficiency promotes the activation of RIPK1 owing to a type of post-translational modification mediated by spermidine and deoxyhyupisin synthase termed acetyl-hypusination. Our results suggest that inhibition of RIPK1 could be used to treat type 2 diabetes and vascular inflammation.

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精胺通过调节 RIPK1 介导的细胞死亡和炎症限制糖尿病的发生

我们在血管内皮细胞中建立了一个由条件性 NAT1 缺乏诱导的进行性糖尿病小鼠模型。NAT1 缺乏会促进 RIPK1 的活化，这是一种由亚精胺和脱氧羽扇豆素合成酶介导的翻译后修饰（称为乙酰化）所致。我们的研究结果表明，抑制 RIPK1 可用于治疗 2 型糖尿病和血管炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.