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APTX4870肽通过抑制源自分枝菌酸诱导的细胞毒性来降低细胞炎症反应的作用。

The role of APTX4870 peptide in reducing cellular inflammatory responses by inhibiting -derived mycolic acid-induced cytotoxicity.

作者信息

Lin Xue, Jia Wei, Feng Gangning, Su Yajing, Kang Yuting, Zhang Chen, Liu Wenmiao, Lu Zhidong, Xue Di

机构信息

Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, China.

Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, China.

出版信息

Front Microbiol. 2022 Oct 24;13:993897. doi: 10.3389/fmicb.2022.993897. eCollection 2022.

DOI:10.3389/fmicb.2022.993897
PMID:36353454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9638010/
Abstract

Tuberculosis is a serious zoonotic disease caused by () and the complex. Mycolic acid is an extracellular carbohydrate polymer produced, secreted, and accumulated outside the cells of various strains. Mycolic acid produced by Mycobacterium plays an important role in infection. However, there have been few reports on drugs that inhibit mycolic acid-induced cytotoxicity. The purpose of this study was to investigate the role of the panned peptide in Mycobacterium-derived mycolic acid (-MA)-induced cell injury. The heptapeptide (APTX4870) was isolated from various phage libraries using phage display (Ph.D-7, Ph.D-12, and Ph.D-C7C). The efficacy of APTX4870 against mycolic acid was demonstrated by evaluating clinical samples and conducting and Vivo. APTX4870 inhibited apoptosis, increased autophagy to decrease inflammation, and reduced -MA-induced lung damage. These findings suggest that this heptapeptide, which selectively targets -MA, might be exploited as a potential novel therapeutic treatment.

摘要

结核病是由（）和复合菌引起的一种严重的人畜共患病。分枝菌酸是由各种菌株在细胞外产生、分泌和积累的一种细胞外碳水化合物聚合物。分枝杆菌产生的分枝菌酸在感染中起重要作用。然而，关于抑制分枝菌酸诱导的细胞毒性的药物报道很少。本研究的目的是探讨淘选肽在分枝杆菌来源的分枝菌酸（-MA）诱导的细胞损伤中的作用。使用噬菌体展示（Ph.D-7、Ph.D-12和Ph.D-C7C）从各种噬菌体文库中分离出七肽（APTX4870）。通过评估临床样本以及进行体内和体外实验，证明了APTX4870对分枝菌酸的疗效。APTX4870抑制细胞凋亡，增加自噬以减轻炎症，并减少-MA诱导的肺损伤。这些发现表明，这种选择性靶向-MA的七肽可能被开发为一种潜在的新型治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/74242b54dc27/fmicb-13-993897-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/d8cbfbf6bbef/fmicb-13-993897-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/7535d9fad6c1/fmicb-13-993897-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/c1a5dc900611/fmicb-13-993897-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/eeb09f550fe2/fmicb-13-993897-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/82fb80304e77/fmicb-13-993897-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/b63204cf701f/fmicb-13-993897-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/7a7dc2c00071/fmicb-13-993897-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/74242b54dc27/fmicb-13-993897-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/d8cbfbf6bbef/fmicb-13-993897-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/7535d9fad6c1/fmicb-13-993897-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/c1a5dc900611/fmicb-13-993897-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/eeb09f550fe2/fmicb-13-993897-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/82fb80304e77/fmicb-13-993897-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/b63204cf701f/fmicb-13-993897-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/7a7dc2c00071/fmicb-13-993897-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3876/9638010/74242b54dc27/fmicb-13-993897-g008.jpg

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