Propofol Protects against Pyroptosis of Photoreceptors in Subretinal Hemorrhage via Regulating SIRT6/NLRP3 Signaling.

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Critical Reviews in Eukaryotic Gene Expression Pub Date : 2025-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2024056605

Huihui Wang, Limei Zhang, Xiaoli Bai, Hao Wang, Hao Sun

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引用次数: 0

Abstract

Subretinal hemorrhage-induced neurotoxicity is a key cause of vision loss in age-related macular degeneration (AMD). The purpose of this study is to investigate the effects of Propofol on neurotoxicity. Oxygen glucose deprivation (OGD) was used to establish in vitro subretinal hemorrhage model. Gene expression was determined using reverse transcription-quantitative polymerase chain reaction and western blot. Cytokine release was determined using enzyme-linked immunosorbent assay. The interaction between sirtuin 6 (SIRT6) and NLR family pyrin domain containing 3 (NLRP3) was detected using co-immunoprecipitation assay. Cellular function was determined using cell counting kit-8 assay, lactate dehydrogenase assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Propofol suppressed the inflammatory response induced by OGD. Moreover, Propofol inhibited the neurotoxicity and pyroptosis of photoreceptors. Propofol mediated the overexpression of SIRT6, which was downregulated in AMD. Inhibition of SIRT6 alleviated its deacetylation of NLRP3. Additionally, SIRT6 deficiency antagonized the effects of Propofol and promoted the neurotoxicity and pyroptosis of photoreceptors. Taken together, Propofol protects against subretinal hemorrhage-induced neurotoxicity and pyroptosis of photoreceptors via promoting SIRT6-mediated deacetylation of NLRP3.

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异丙酚通过调节SIRT6/NLRP3信号传导抑制视网膜下出血中的光感受器焦亡。

视网膜下出血引起的神经毒性是老年性黄斑变性（AMD）中视力丧失的主要原因。本研究旨在探讨异丙酚对神经毒性的影响。采用氧葡萄糖剥夺法（OGD）建立离体视网膜下出血模型。采用逆转录-定量聚合酶链反应和western blot检测基因表达。采用酶联免疫吸附法测定细胞因子释放量。采用共免疫沉淀法检测SIRT6 （SIRT6）与NLR家族pyrin domain containing 3 （NLRP3）的相互作用。采用细胞计数试剂盒-8法、乳酸脱氢酶法和末端脱氧核苷酸转移酶dUTP缺口末端标记法测定细胞功能。异丙酚抑制OGD诱导的炎症反应。此外，异丙酚抑制了光感受器的神经毒性和焦亡。异丙酚介导SIRT6过表达，而SIRT6在AMD中下调。抑制SIRT6可减轻其对NLRP3的去乙酰化。此外，SIRT6缺乏可拮抗异丙酚的作用，促进光感受器的神经毒性和焦亡。综上所述，异丙酚通过促进sirt6介导的NLRP3去乙酰化来防止视网膜下出血诱导的神经毒性和光感受器焦亡。

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

Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物

CiteScore

2.70

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.