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Abstract: End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis B, are often combined with 28hepatic encephalopathy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>hepatic encephalopathy (HE); ammonia poisoning is posited as one of its main pathogenesis mechanisms. Ammonia is closely related to 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>autophagy, but the molecular mechanism of ammonia’s regulatory effect on 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>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. 28ST3 ;2%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>ST3 ;2;‍28-galactoside α%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>-galactoside α;2,‍3-sialyltransferase 6 (ST3GAL6) is one of the significant glycosyltransferases responsible for adding α2,3-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 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>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 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>autophagy in HE. Therefore, we aimed to determine the regulatory relationship between ST3GAL6 and 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>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 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>autophagy. In addition, silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein ;2;8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). Notably, the overexpression of HSPB8 partially restored the reduced 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>autophagy levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 regulates 28autophagy%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>2f4a8b>autophagy through the HSPB8-BAG3 complex.

唾液酸糖基转移酶ST3GAL6的沉默可通过减少α2,3-唾液酸化聚糖降低HSPB8-BAG3表达从而调控肝性脑病小鼠大脑中的自噬

[1]AbdullahML,Al-ShabanahO,HassanZK,et al.,2021.Eugenol-induced autophagy and apoptosis in breast cancer cells via PI3K/AKT/FOXO3a pathway inhibition.Int J Mol Sci,22(17):9243.

[2]BaoT,KarimN,KeHH,et al.,2023.Polysaccharide isolated from wax apple suppresses ethyl carbamate-induced oxidative damage in human hepatocytes.J Zhejiang Univ-Sci B (Biomed & Biotechnol),24(7):574-586.

[3]BarmakiH,NourazarianA,Khaki-KhatibiF,2023.Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer’s disease.Front Aging Neurosci,15:1281338.

[4]BowlesWHD,GlosterTM,2021.Sialidase and sialyltransferase inhibitors: targeting pathogenicity and disease.Front Mol Biosci,8:705133.

[5]ChierichettiM,CerretaniM,CiammaichellaA,et al.,2023.Identification of HSPB8 modulators counteracting misfolded protein accumulation in neurodegenerative diseases.Life Sci,322:121323.

[6]DaiH,HuWJ,ZhangLY,et al.,2021.FGF21 facilitates autophagy in prostate cancer cells by inhibiting the PI3K‒Akt‒mTOR signaling pathway. Cell Death Dis,12(4):303.

[7]DalangoodS,ZhuZ,MaZH,et al.,2020.Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer.Theranostics,10(22):‍10078-10091.

[8]FallahzadehMA,RahimiRS,2022.Hepatic encephalopathy: current and emerging treatment modalities.Clin Gastroenterol Hepatol,20(S8):S9-S19.

[9]FilipponeA,EspositoE,ManninoD,et al.,2022.The contribution of altered neuronal autophagy to neurodegeneration.Pharmacol Ther,238:108178.

[10]FriedmanJ,2011.Why is the nervous system vulnerable to oxidative stress? In: Gadoth N, Göbel HH (Eds.),Oxidative Stress and Free Radical Damage in Neurology.Springer, Totowa, p.19-27.

[11]HuJL,ShanYJ,MaJ,et al.,2019.LncRNA ST3Gal6‐AS1/ST3Gal6 axis mediates colorectal cancer progression by regulating α‍‐‍2,‍3 sialylation via PI3K/Akt signaling.Int J Cancer,145(2):450-460.

[12]HuangJJ,BaiYM,XieWT,et al.,2023.Lycium barbarum polysaccharides ameliorate canine acute liver injury by reducing oxidative stress, protecting mitochondrial function, and regulating metabolic pathways.J Zhejiang Univ-Sci B (Biomed & Biotechnol),24(2):157-171.

[13]HuangJM,HuangJM,ZhangGN,2022.Insights into the role of sialylation in cancer metastasis, immunity, and therapeutic opportunity.Cancers,14(23):5840.

[14]Kim CH,2020.Sialyltransferase,sialylation, andsulfoylation. In: Kim CH (Ed.), Ganglioside Biochemistry.Springer,Singapore, p.35-53.

[15]KwonY,HaamCE,ByeonS,et al.,2022.Effects of 3-methyladenine, an autophagy inhibitor, on the elevated blood pressure and arterial dysfunction of angiotensin II-induced hypertensive mice.Biomed Pharmacother,154:113588.

[16]LawrenceJM,SchardienK,WigdahlB,et al.,2023.Roles of neuropathology-associated reactive astrocytes: a systematic review.Acta Neuropathol Commun,11:42.

[17]LiFJ,DingJJ,2019.Sialylation is involved in cell fate decision during development, reprogramming and cancer progression.Protein Cell,10(8):550-565.

[18]LiHS,YouLK,XieJS,et al.,2017.The roles of subcellularly located EGFR in autophagy.Cell Signal,35:223-230.

[19]LiJX,LongYM,SunJY,et al.,2022.Comprehensive landscape of the ST3GAL family reveals the significance of ST3GAL6-AS1/ST3GAL6 axis on EGFR signaling in lung adenocarcinoma cell invasion.Front Cell Dev Biol,10:931132.

[20]LinH,KorenSA,CvetojevicG,et al.,2022.The role of BAG3 in health and disease: a “Magic BAG of Tricks”.J Cell Biochem,123(1):4-21.

[21]LuKH,ZimmermannM,GörgB,et al.,2019.Hepatic encephalopathy is linked to alterations of autophagic flux in astrocytes.eBioMedicine,48:539-553.

[22]MareninovaOA,JiaWZ,GretlerSR,et al.,2020.Transgenic expression of GFP-LC3 perturbs autophagy in exocrine pancreas and acute pancreatitis responses in mice.Autophagy,16(11):2084-2097.

[23]Ochoa-SanchezR,TamnanlooF,RoseCF,2021.Hepatic encephalopathy: from metabolic to neurodegenerative.Neurochem Res,46(10):2612-2625.

[24]ParkH,KangJH,LeeS,2020.Autophagy in neurodegenerative diseases: a hunter for aggregates.Int J Mol Sci,21(9):3369.

[25]PekerN,GozuacikD,2020.Autophagy as a cellular stress response mechanism in the nervous system.J Mol Biol,432(8):2560-2588.

[26]QiF,IsajiT,DuanCW,et al.,2020.ST3GAL3, ST3GAL4, and ST3GAL6 differ in their regulation of biological functions via the specificities for the α2,‍3‍‐‍sialylation of target proteins. FASEB J,34(1):881-897.

[27]RoseCF,AmodioP,BajajJS,et al.,2020.Hepatic encephalopathy: novel insights into classification, pathophysiology and therapy.J Hepatol,73(6):1526-1547.

[28]SeidelK,VinetJ,den DunnenWFA,et al.,2012.The HSPB8‐BAG3 chaperone complex is upregulated in astrocytes in the human brain affected by protein aggregation diseases.Neuropathol Appl Neurobiol,38(1):39-53.

[29]SepehrinezhadA,ZarifkarA,NamvarG,et al.,2020.Astrocyte swelling in hepatic encephalopathy: molecular perspective of cytotoxic edema.Metab Brain Dis,35(4):‍559-578.

[30]ShenY,MalikSA,AmirM,et al.,2020.Decreased hepatocyte autophagy leads to synergistic IL‐1β and TNF mouse liver injury and inflammation.Hepatology,72(2):595-608.

[31]SiddiquiSS,MatarR,MerhebM,et al.,2019.Siglecs in brain function and neurological disorders.Cells,8(10):1125.

[32]SoriaLR,Brunetti-PierriN,2019.Ammonia and autophagy: an emerging relationship with implications for disorders with hyperammonemia.J Inherit Metab Dis,42(6):1097-1104.

[33]SunMM,ZhaoXZ,LiangLL,et al.,2017.Sialyltransferase ST3GAL6 mediates the effect of microRNA-26a on cell growth, migration, and invasion in hepatocellular carcinoma through the protein kinase B/mammalian target of rapamycin pathway.Cancer Sci,108(2):267-276.

[34]TangHY,HuangHY,WangD,et al.,2022.TFEB ameliorates autophagy flux disturbance induced by PBDE-47 via up-regulating autophagy-lysosome fusion.J Hazard Mater,430:128483.

[35]TogawaJ,OhiT,YuanJH,et al.,2019.Atypical familial amyotrophic lateral sclerosis with slowly progressing lower extremities-predominant late-onset muscular weakness and atrophy.Intern Med,58(13):1851-1858.

[36]UenoT,KomatsuM,2020.Monitoring autophagy flux and activity: principles and applications.BioEssays,42(11):2000122.

[37]VishwakarmaJ,GuptaK,MishraJ,et al.,2023.Hypothyroidism induces motor deficit via altered cerebellar HB-EGF/EGFR and autophagy.J Endocrinol,257(1):e220338.

[38]XuK,HeYZ,MoqbelSAA,et al.,2021.SIRT3 ameliorates osteoarthritis via regulating chondrocyte autophagy and apoptosis through the PI3K/Akt/mTOR pathway.Int J Biol Macromol,175:351-360.

[39]YangKK,YangZF,ChenXF,et al.,2021.The significance of sialylation on the pathogenesis of Alzheimer’s disease.Brain Res Bull,173:116-123.

[40]ZhangX,DongZ,FanH,et al.,2023.Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-‍κB pathways. J Zhejiang Univ-Sci B (Biomed & Biotechnol),24(7):617-631.