Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy  

作　　者：Xiaocheng LI Yaqing XIAO Pengfei LI Yayun ZHU Yonghong GUO Huijie BIAN Zheng LI 

机构地区：[1]Laboratory for Functional Glycomics,College of Life Sciences,Northwest University,Xi’an 710069,China [2]National Translational Science Center for Molecular Medicine,Department of Cell Biology,Fourth Military Medical University,Xi’an 710032,China [3]Medical Experiment Center,Shaanxi University of Chinese Medicine,Xianyang 712046,China [4]The Infectious Disease Department,Gongli Hospital,Pudong New Area,Shanghai 200135,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第6期485-498,共14页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(No.82370592);the Discipline Construction Project of the Health System in Pudong New Area(No.PWZbr2022-15);the Pudong New Area Special Fund for Livelihood Research Project of Science and Technology Development Fund(No.PKJ2021-Y12),China.

摘　　要：End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia’s regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for addingα2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-II(MAL-II)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock proteinβ8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

关 键 词：Hepatic encephalopathy HYPERAMMONEMIA AUTOPHAGY ST3β-galactosideα2 3-sialyltransferase 6(ST3GAL6) Heat shock proteinβ8(HSPB8) 

分 类 号：R575[医药卫生—消化系统] R747.9[医药卫生—内科学]