黄芩苷减轻糖尿病动脉粥样硬化中高糖诱导的焦亡:nrf2 - fbxl2介导的NLRP3降解的作用

IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM
Qingxin Meng, Yongpan Huang, Xian Long, Lijing Liu, Yani Tang, Jingjing He, Yayuan Luo
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引用次数: 0

摘要

本研究探讨了黄芩苷(Scu)和Nrf2在糖尿病动脉粥样硬化中的作用,重点研究了它们对FBXL2和NLRP3泛素化的影响。采用高糖处理人脐静脉内皮细胞,建立糖尿病动脉粥样硬化体外模型。评估细胞活力、细胞毒性、焦亡和炎症细胞因子水平,并通过双荧光素酶报告基因检测检测基因相互作用。通过免疫沉淀和免疫印迹分析泛素化和蛋白水平。结果显示,HG处理可降低Nrf2和FBXL2水平,增强nlrp3介导的焦亡。然而,Scu处理增加了Nrf2的表达,提高了细胞活力,并抑制了焦亡。Nrf2敲低可下调FBXL2,逆转Scu的保护作用。此外,FBXL2促进泛素化介导的NLRP3降解,抑制焦亡。NLRP3的激活逆转了Scu对糖尿病动脉粥样硬化的保护作用。这些结果表明,Scu通过增加Nrf2和FBXL2的表达,促进NLRP3泛素化介导的降解,抑制焦亡来缓解糖尿病动脉粥样硬化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Scutellarin mitigates high glucose-induced pyroptosis in diabetic atherosclerosis: Role of Nrf2-FBXL2-mediated NLRP3 degradation.

This study investigated the role of scutellarin (Scu) and Nrf2 in diabetic atherosclerosis, focusing on their effects on FBXL2 and NLRP3 ubiquitination. Human umbilical vein endothelial cells were treated with high glucose (HG) to model diabetic atherosclerosis in vitro. Cell viability, cytotoxicity, pyroptosis, and inflammatory cytokine levels were assessed, and gene interactions were examined by dual-luciferase reporter assays. Ubiquitination and protein levels were analyzed through immunoprecipitation and western blotting. The results revealed that HG treatment decreased Nrf2 and FBXL2 levels and enhanced NLRP3-mediated pyroptosis. However, Scu treatment increased Nrf2 expression, improved cell viability, and inhibited pyroptosis. Nrf2 knockdown downregulated FBXL2 and reversed the protective effects of Scu. Additionally, FBXL2 promoted the ubiquitination-mediated degradation of NLRP3 and suppressed pyroptosis. The activation of NLRP3 reversed the protective effects of Scu on diabetic atherosclerosis. These findings suggest that Scu alleviated diabetic atherosclerosis by increasing Nrf2 and FBXL2 expression, promoting NLRP3 ubiquitination-mediated degradation, and suppressing pyroptosis.

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来源期刊
Endocrine journal
Endocrine journal 医学-内分泌学与代谢
CiteScore
4.30
自引率
5.00%
发文量
224
审稿时长
1.5 months
期刊介绍: Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.
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