Desialylation of ATG5 by sialidase (NEU1) promotes macrophages autophagy and exacerbates inflammation under hypoxia

作者全名："Zeng, Shengmei; Wen, Yilin; Yu, Chao"

作者地址："[Zeng, Shengmei; Wen, Yilin; Yu, Chao] Chongqing Med Univ, Coll Pharm, Chongqing 400016, Peoples R China; [Zeng, Shengmei; Wen, Yilin; Yu, Chao] Chongqing Key Lab Pharmaceut Metab Res, Chongqing 400016, Peoples R China; [Yu, Chao] Chongqing Med Univ, Chongqing Key Lab Drug Metab Res, 1 Med Coll Rd, Chongqing 400016, Peoples R China"

通信作者："Yu, C (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Drug Metab Res, 1 Med Coll Rd, Chongqing 400016, Peoples R China."

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001096478700001

JCR分区：Q2

影响因子：4.4

年份：2023

卷号：112

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Hypoxia; Autophagy; NEU1; ATG5; Sialylation; Macrophages

摘要："During the process of atherosclerosis (AS), hypoxia induces plaque macrophage inflammation, promoting lipid accumulation. Autophagy is a cell homeostasis process that increases tolerance to stressors like oxidative stress and hypoxia. However, the specific mechanism by which hypoxia initiates autophagy and the inflammation of macrophages remains to be elucidated. Here, we found that hypoxia-induced macrophage inflammation was mediated by autophagy. Then, the effect of hypoxia on autophagy was investigated in terms of post-translational modifications of proteins. The results showed that desialylation of the autophagy protein ATG5 under hypoxic conditions enhanced protein stability by affecting its charge effect and promoted the formation of the ATG5ATG12-ATG16L complex, further increasing autophagosome formation. And NEU1, a key enzyme in sialic acid metabolism, was significantly up-regulated under hypoxic conditions and was identified as an interacting protein of ATG5, affecting the sialylation of ATG5. In addition, the knockdown or inhibition of NEU1 reversed hypoxia-induced autophagy and inflammatory responses. In conclusion, our data reveal a key mechanism of autophagy regulation under hypoxia involving ATG5 sialylation and NEU1, suggesting that NEU1 may be a potential target for the prevention and treatment of atherosclerosis."

基金机构：Chongqing key project of technological innovation and application development [cstc2020jscx-msx mX0070]; Chongqing talent plan [CQYCC201903166]

基金资助正文："This work was supported in part by Chongqing key project of technological innovation and application development (cstc2020jscx-msx mX0070), Chongqing talent plan (CQYCC201903166)."