A combined metabolomics and molecular biology approach to reveal hepatic injury and underlying mechanisms after chronic L-lactate exposure in mice

doi:10.1016/j.csbj.2022.07.034

科研成果详情

题名	A combined metabolomics and molecular biology approach to reveal hepatic injury and underlying mechanisms after chronic L-lactate exposure in mice
作者	Dong, Minjian 1; Yi, Qingqing1; Shen, Danjie1; Yan, Jiapin1; Jiang, Haowei 1; Xie, Jiaojiao1; Zhao, Liangcai1; Gao, Hongchang1,2
发表日期	2022
发表期刊	Computational and Structural Biotechnology Journal 影响因子和分区
语种	英语
原始文献类型	Journal article (JA)
关键词	Amino acids Histology Mammals Metabolism Molecular biology Nuclear magnetic resonance Plants (botany) Polymerase chain reaction Superoxide dismutase Tissue C57BL/6 mice Hepatic injury Hepatic tissue L-lactate Metabolic changes Metabolomics Organ functions Peripheral tissue Reactive oxygen species Serum samples
其他关键词	EXERCISE ; METABOLISM ; EXPRESSION ; NEURONS ; MUSCLE ; BRAIN ; CELLS ; LIVER ; SERUM ; MODEL
摘要	This study aimed to explore whether chronic L-lactate exposure could affect the peripheral tissues of mice and to determine the underlying pathogenesis. Herein, male C57BL/6 mice were divided into control and L-lactate groups. After L-lactate treatment for eight weeks (1 g/kg), metabolic changes in liver, kidney, muscle, and serum samples were determined by 1H nuclear magnetic resonance (1H NMR)-based metabolomics. Additionally, organ function was evaluated by serum biochemical and histopathological examinations. Reactive oxygen species (ROS) levels were measured using dihydroethidium staining; levels of signals involved in lactate metabolism and ROS-related pathways were detected using western blotting or polymerase chain reaction. Apoptosis was detected by TUNEL-fluorescence staining. Metabolomic analysis revealed that L-lactate mice showed decreased levels of glutathione (GSH), taurine, ATP, and increased glucose content, compared to control mice. Furthermore, L-lactate mice presented significantly higher serum levels of alanine aminotransferase and aspartate aminotransferase and increased glycogen content in hepatic tissues, compared to control mice. L-lactate mice also had a greater number of apoptotic nuclei in the livers than controls. Moreover, L-lactate exposure reduced mRNA and protein levels of superoxide dismutase-2 and c-glutamylcysteine ligase, elevated levels of cytochrome P450 2E1 and NADPH oxidase-2, and increased the protein expressions of LDHB, Bax/Bcl-2, cleaved caspase-3, and sirtuin-1 in hepatic tissues. Together, these results indicate that chronic L-lactate exposure increases oxidative stress and apoptosis in hepatocytes via upregulation of Bax/Bcl-2 expression and the consequent mitochondrial cytochrome-C release and caspase-3 activation, which contributes to the pathogenesis of hepatic dysfunction. © 2022 The Author(s)
资助项目	Natural Science Foundation of Zhejiang Province [LY22H070003]; National Natural Science Foundation of China [81770830]
出版者	Elsevier B.V.
出版地	AMSTERDAM
ISSN	2001-0370
EISSN	2001-0370
卷号	20 页码:3935-3945
DOI	10.1016/j.csbj.2022.07.034
页数	11
WOS类目	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology
WOS研究方向	Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology
WOS记录号	WOS:000889723800004
收录类别	EI ; PUBMED ; SCIE ; SCOPUS
EI入藏号	20223112456553
EI主题词	Cell death
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.9 Biology ; 801.2 Biochemistry ; 804.1 Organic Compounds
URL	查看原文
PubMed ID	35950184
SCOPUSEID	2-s2.0-85134885862
通讯作者地址	[Zhao, Liangcai]School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Biotechnology;Biophysics;Structural Biology;Biochemistry;Genetics;Computer Science Applications
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/153448
专题	药学院（分析测试中心）卓越中心_老年研究院
通讯作者	Zhao, Liangcai
作者单位	1.School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),Key Laboratory of Alzheimer's Disease of Zhejiang Province,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Dong, Minjian,Yi, Qingqing,Shen, Danjie,et al. A combined metabolomics and molecular biology approach to reveal hepatic injury and underlying mechanisms after chronic L-lactate exposure in mice[J]. Computational and Structural Biotechnology Journal,2022,20:3935-3945.
APA	Dong, Minjian., Yi, Qingqing., Shen, Danjie., Yan, Jiapin., Jiang, Haowei., ... & Gao, Hongchang. (2022). A combined metabolomics and molecular biology approach to reveal hepatic injury and underlying mechanisms after chronic L-lactate exposure in mice. Computational and Structural Biotechnology Journal, 20, 3935-3945.
MLA	Dong, Minjian,et al."A combined metabolomics and molecular biology approach to reveal hepatic injury and underlying mechanisms after chronic L-lactate exposure in mice".Computational and Structural Biotechnology Journal 20(2022):3935-3945.