Chemo-proteomics reveals dihydrocaffeic acid exhibits anti-inflammation effects via Transaldolase 1 mediated PERK-NF-κB pathway.

IF 8.2 2区生物学 Q1 CELL BIOLOGY Cell Communication and Signaling Pub Date : 2025-02-05 DOI:10.1186/s12964-024-01958-3

Guanjun Li, Huiying Li, Peili Wang, Xinzhou Zhang, Wenhua Kuang, Ling Huang, Ying Zhang, Wei Xiao, Qingfeng Du, Huan Tang, Jigang Wang

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Abstract

Background: Acute pneumonia is a kind of widespread inflammatory pathological process. Dihydrocaffeic acid (DA), metabolite of chlorogenic acid, possesses potent pharmacologic activity for the therapy of a wide range of disorders and various biological properties, such as anti-inflammation. Nevertheless, the specific protein targets and potential molecular mechanisms of DA in acute pneumonia are still poorly understood.

Purpose: To investigate the anti-inflammation effects of DA and its target and its specific mechanisms.

Methods: Here, we conducted lipopolysaccharides (LPS)-induced acute pneumonia model mice. Besides, the activity-based protein profiling (ABPP) was performed to explore the potential targets of DA. Furthermore, cellular thermal shift assay (CETSA) and pulldown-western blot assays were used to validate the conclusion.

Results: In this study, we indicated that DA alleviated acute pneumonia in mice and displayed excellent anti-inflammatory efficacy in vivo and in vitro. Besides, we discovered DA binds directly to transaldolase 1(TALDO1) and influenced its enzymatic activity, and identified the specific cysteine sites Cys250. Also we demonstrated that DA reveals anti-inflammation effect through TALDO1 mediated PERK-IκBα-NF-κB pathway in RAW 264.7 cells.

Conclusion: This study provide support for the potential advancement of DA for use as a therapeutic agent for the treatment of acute pneumonia and inflammation-associated diseases.

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化学蛋白质组学显示，二氢咖啡酸通过转醛缩酶1介导的PERK-NF-κB通路具有抗炎作用。

背景：急性肺炎是一种广泛存在的炎症病理过程。二氢咖啡酸（DA）是绿原酸的代谢物，具有治疗多种疾病和多种生物学特性的有效药理活性，如抗炎。然而，DA在急性肺炎中的特异性蛋白靶点和潜在的分子机制仍然知之甚少。目的：探讨DA的抗炎作用及其靶点及其特异性机制。方法：采用脂多糖（LPS）诱导的急性肺炎模型小鼠。此外，我们还进行了基于活性的蛋白谱分析（ABPP）来探索DA的潜在靶点。此外，采用细胞热移法（CETSA）和下拉-western blot法验证结论。结果：在本研究中，我们发现DA能减轻小鼠急性肺炎，并在体内和体外均表现出良好的抗炎作用。此外，我们发现DA直接与转醛dolase 1（TALDO1）结合并影响其酶活性，并鉴定了特异性半胱氨酸位点Cys250。我们还发现DA在RAW 264.7细胞中通过TALDO1介导的perk -i -κB α- nf -κB通路发挥抗炎作用。结论：本研究为DA作为一种治疗急性肺炎和炎症相关疾病的药物提供了潜在的支持。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.