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The protective effect of uric acid in reducing TLR4/NF-κB activation through the inhibition of HMGB1 acetylation in a model of ischemia-reperfusion injury in vitro
- Source :
- Molecular biology reports. 47(4)
- Publication Year :
- 2019
-
Abstract
- Inflammation plays an important role in ischemia–reperfusion injury. Through its antioxidative effects, uric acid can reduce cell injury. However, its mechanism is unknown. This study investigated the protective mechanism of uric acid in cells during ischemia–reperfusion. We divided hippocampal neurons into six groups: the control, OGD, OGD/R, OGD/R + HMGB1 siRNA, OGD/R + uric acid, and OGD/R + uric acid + HMGB1 groups. The MTT assay was used to evaluate cell viability, while apoptosis was detected by flow cytometry. The expression of HMGB1, TLR4, NF-κB-p65 and phosphorylated NF-κB-p65 was detected by Western blotting. The levels of IL-6, IL-1β and TNF-α in the culture medium were determined by ELISA. The results indicated increased cell viability and decreased apoptosis in the presence of HMGB1 siRNA and uric acid but the opposite findings in the presence of HMGB1 protein after OGD/R. Uric acid and HMGB1 siRNA inhibited HMGB1 acetylation to prevent its transport from the nucleus to the cytoplasm. The expression of HMGB1 downstream proteins (TLR4, NF-κB-p65 and phosphorylated NF-κB-p65) and the levels of inflammatory factors in the presence of HMGB1 siRNA and uric acid was lower than those in the presence of HMGB1 protein after OGD or OGD/R. These data indicated that uric acid may prevent cell injury mainly by inhibiting HMGB1 acetylation to regulate TLR4/NF-κB pathways and reduce the levels of inflammatory factors.
- Subjects :
- 0301 basic medicine
chemical and pharmacologic phenomena
Inflammation
Apoptosis
Pharmacology
HMGB1
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Genetics
medicine
Animals
MTT assay
Viability assay
HMGB1 Protein
Molecular Biology
biology
Tumor Necrosis Factor-alpha
NF-kappa B
Transcription Factor RelA
Acetylation
General Medicine
medicine.disease
Uric Acid
carbohydrates (lipids)
Toll-Like Receptor 4
030104 developmental biology
nervous system
chemistry
Gene Expression Regulation
030220 oncology & carcinogenesis
Reperfusion Injury
TLR4
biology.protein
Uric acid
medicine.symptom
Reperfusion injury
Signal Transduction
Subjects
Details
- ISSN :
- 15734978
- Volume :
- 47
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular biology reports
- Accession number :
- edsair.doi.dedup.....6365c234d7aa982ca032ef55fb3ed7b7