Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition

Autor: Tadayuki Ikeda, Yaiko Hara, Tetsuji Sato, Kenjiro Wake, Kouji Inoue, Noriyuki Kuroda
Rok vydání: 2014
Předmět:
Lipopolysaccharides
Male
Time Factors
Receptor for Advanced Glycation End Products
Apoptosis
Galactosamine
Biochemistry
chemistry.chemical_compound
Cell Signaling
Molecular Cell Biology
Gene expression
HMGB1 Protein
Promoter Regions
Genetic
Glutathione Transferase
Liver injury
Mice
Inbred BALB C
Multidisciplinary
Protein translation
Acetylation
Alanine Transaminase
General Medicine
Transport protein
Protein Transport
Medicine
Anatomy
medicine.symptom
General Agricultural and Biological Sciences
Protein Binding
Research Article
Signal Transduction
Histology
Kupffer Cells
Science
DNA transcription
chemical and pharmacologic phenomena
Inflammation
Biology
HMGB1
Histone Deacetylases
General Biochemistry
Genetics and Molecular Biology
DNA-binding proteins
Genetics
medicine
Extracellular
Animals
Aspartate Aminotransferases
RNA
Messenger
Glycyrrhizin
Biology and life sciences
Proteins
Dendritic Cells
Cell Biology
Glycyrrhizic Acid
medicine.disease
Molecular biology
Toll-Like Receptor 4
Gene Expression Regulation
chemistry
biology.protein
Transcriptional Signaling
Carrier Proteins
Extracellular Space
Liver Failure
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 4, p e92884 (2014)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0092884
Popis: HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality. In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury. At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated. Administration of LPS/GalN precipitated tissue injury associated with time-dependent alteration in HMGB1 serum levels. At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci. The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine. Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method. On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR. The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL. The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence.
Databáze: OpenAIRE
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