Caspase-1 Cleavage of Aldolase B Impairs Hepatic Fructose Metabolism and Aggravates Chronic Viral Hepatitis  

作　　者：Hong Tang Haiming Hu Yanhang Gao Zhilong Wang Feng Yuan Chao Zhang Sisi Deng Pingyun Lyu Jingying Zhan Chengkai Li Hairong Chen Junqi Niu 

机构地区：[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [2]Wuhan Institute of Virology,Chinese Academy of Sciences,Hubei,China [3]Department of Hepatology,The First Hospital of Jilin University,Changchun,China [4]Shanghai Institute of Immunity and Infection,Chinese Academy of Sciences,Shanghai,China [5]Institute of Biophysics,Chinese Academy of Sciences,Beijing,China

出　　处：《Infectious Microbes & Diseases》2024年第2期74-84,共11页感染微生物与疾病（英文）

基　　金：the National Natural Science Foundation of China(81530067,31621061,31300716);the Ministry of Science and Technology(2015CB554304);the Hubei Provincial Natural Science Foundation(2013CFB487);Shandong Laboratory Microecological Biomedicine(JNL-2023002B);the Fundamental Research Funds for the Central Universities(2022ZFJH003).

摘　　要：Of dietary monosaccharides,fructose is primarily metabolized by aldolase B(ALDOB)in the liver,whereas glucose is metabolized elsewhere in the body.It has been documented that overconsumption of dietary fructose,especially industrial fructose,associates significantly with advanced inflammation in chronic hepatitis C(CHC)patients.However,little is known about whether impaired fructolysis might attribute to CHC hepatopathogenesis.Herein we found that the level of ALDOB protein was significantly reduced in CHC patients and mice that were persistently infected by hepatitis C virus(HCV).In vitro,HCV infection activated caspase-1,and caspase-3 to a lesser extent,which proteolyzed ALDOB and blocked fructose metabolism in hepatocytes.Downregulation of ALDOB attenuated HCV replication,indicating an intrinsic anti-HCV role for homeostatic fructolysis.On the other hand,reduced ALDOB caused intracellular fructose 1-phosphate accumulation that provoked severe cellular toxicity through intracellular ATP depletion and heightened glycation,which was aggravated by HCV infection.Taken together,these results have unveiled that inflammatory activation of caspase-1 impairs homeostatic fructolysis and exacerbates liver damage.

关 键 词：ALDOB fructose metabolism CASPASE-1 HCV 

分 类 号：R512.6[医药卫生—内科学]