秀丽隐杆线虫中β-N-乙酰氨基葡萄糖苷酶的下调可提高应激适应性。

Downregulation of Endo-Beta-N-Acetylglucosaminidase in Caenorhabditis elegans Improves Stress Adaptivity.

作者信息

Lu Xinrong, Tong Yongliang, Wu Mengting, Lyu Shaoxian, Fan Jiale, Zheng Junyu, Zou Lin, Shen Danfeng, Rao Lin, Hou Linlin, Chen Cuiying, Cheng Xunjia, Sun Guiqin, Shao Zhiyong, Chen Li

机构信息

Department of Medical Microbiology, Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical Sciences, Fudan University, Translational Glycomics Research Center, Fudan Zhangjiang Institute, Shanghai, China,

出版信息

Cells Tissues Organs. 2025 May 10:1-15. doi: 10.1159/000546244.

DOI:10.1159/000546244

PMID:40349683

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12187103/

Abstract

INTRODUCTION

Endo-beta-N-acetylglucosaminidase (ENGASE) is one of the key enzymes involved in the structural and functional regulations of glycoproteins. Although its enzymatic activities and applications have been well studied in vitro, its biological function in vivo yet remains to be illustrated. In this study, the biological function of ENGASE in Caenorhabditis elegans was explored in detail.

METHODS

An Engase gene knockout in C. elegans (CeEng-1 or CeEngase) was constructed and subjected to a panel of phenotypical and glycomics analysis. In addition, in vitro and in vivo ENGASE inhibition assays were performed.

RESULTS

Engase knockout worm's adaptivity to environmental stresses (heat and osmotic) was significantly improved, and its longevity was also increased mildly. A clustered change in basement membrane proteins (e.g., LAM-1, LAM-2, and EPI-1) was illustrated by N-glycopeptide analysis, suggesting that ENGASE is involved in a basement membrane-based stress regulation. Then, the heat stress phenotype was further supported by in vivo CeEngase knockdown assay and in vitro and in vivo small compound inhibitory assay of CeENGASE, indicating that ENGASE is a potential drug target for stress management.

CONCLUSION

Engase is actively involved in a basement membrane-mediated stress adaptation and could serve as a potential target for healthcare products.

摘要

引言

内切β-N-乙酰氨基葡萄糖苷酶（ENGASE）是参与糖蛋白结构和功能调节的关键酶之一。尽管其酶活性和应用在体外已得到充分研究，但其在体内的生物学功能仍有待阐明。在本研究中，详细探讨了ENGASE在秀丽隐杆线虫中的生物学功能。

方法

构建了秀丽隐杆线虫（CeEng-1或CeEngase）中的Engase基因敲除品系，并进行了一系列表型和糖组学分析。此外，还进行了体外和体内ENGASE抑制试验。

结果

Engase基因敲除的线虫对环境应激（热应激和渗透应激）的适应性显著提高，其寿命也略有延长。N-糖肽分析表明基底膜蛋白（如LAM-1、LAM-2和EPI-1）发生了聚集性变化，提示ENGASE参与基于基底膜的应激调节。然后，体内CeEngase基因敲低试验以及CeENGASE的体外和体内小分子化合物抑制试验进一步支持了热应激表型，表明ENGASE是应激管理的潜在药物靶点。