Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

Autor: Eun Ju Im, Pyong Gon Moon, Esteban Mezey, Byoung Joon Song, Young-Eun Cho, Moon-Chang Baek
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Proteomics
Cell Membranes
lcsh:Medicine
Social Sciences
Pharmacology
Biochemistry
chemistry.chemical_compound
Mice
Animal Cells
Medicine and Health Sciences
Psychology
Enzyme-Linked Immunoassays
lcsh:Science
Liver injury
Multidisciplinary
Hep G2 Cells
Animal Models
Middle Aged
Blood proteins
Addicts
Immunoblot Analysis
Liver
Experimental Organism Systems
Female
Thioacetamide
Chemical and Drug Induced Liver Injury
Cellular Types
Anatomy
Cellular Structures and Organelles
medicine.drug
Research Article
Adult
Alcoholic hepatitis
Addiction
Molecular Probe Techniques
Mouse Models
Research and Analysis Methods
03 medical and health sciences
Extracellular Vesicles
Model Organisms
medicine
Animals
Humans
Aspartate Aminotransferases
Alcoholics
Immunoassays
Molecular Biology Techniques
Molecular Biology
Hepatitis
Plasma Proteins
Hepatitis
Alcoholic
lcsh:R
Biology and Life Sciences
Proteins
Membrane Proteins
Bilirubin
Cell Biology
medicine.disease
Molecular biology
Acetaminophen
Transplantation
030104 developmental biology
chemistry
Membrane protein
Hepatocytes
Immunologic Techniques
lcsh:Q
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 2, p e0172463 (2017)
PLOS ONE(12): 2
ISSN: 1932-6203
Popis: Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity.
Databáze: OpenAIRE
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