Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway
Abstract
:1. Introduction
2. Results
2.1. Furosine Increases the Expressios of Liver Biochemical Indicators
2.2. Furosine Exerts and Adverse Effect on the Liver
2.3. Transcriptomics Analysis of Furosine Metabolites in Liver Tissue, Serum, and Red Blood Cells
2.4. Screening of Specific Metabolites in Liver Tissue, Serum, and RBC
2.5. Furosine Enhanced the Expression of PLA2-3, RIPK-1, RIPK-3, P-MLKL, TNF-α, and IL-1β in Liver Tissue and Primary Hepatocytes
3. Discussion
4. Materials and Methods
4.1. Mice Chronic Toxicity Model
4.2. Histopathologial Test
4.3. Biochemical Analysis
4.4. Sample Preparation for Metabonomics Analysis
4.5. Quantitative Real-Time PCR (q-PCR) Analysis
4.6. Primary Hepatocyte Separation and Culture
4.7. Cell Viability Detection
4.8. Cell siRNA Treatment
4.9. Protein Sample Preparation and Western Blot Detection
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
MRP | Maillard reaction product |
LPC (18:0) | lysophosphatidylcholine 18:0 |
PLA2-3 | phospholipase A2 gamma |
RIPK1 | receptor-interacting serine/threonine-protein kinase 1 |
RIPK3 | receptor-interacting serine/threonine-protein kinase 3 |
MLKL | mixed lineage kinase domain-like protein |
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Gene Name | Primer Sequences (5′→3′) | |
---|---|---|
Forward Primer | Reverse Primer | |
PLA2-3 | CCGCAGAGAAGAAGGAGCAGTT | CACGCACAGGAGGCAGAACA |
RIPK-1 | TGAAGCCCACAGCGATTCTT | GCCATCTTTCTCCCCCAAGA |
RIPK-3 | ACATGCATGGTCATGCACACACAT | TTGAGACATCTCTTTTTGGAG |
MLKL | CCCGAGTTGTTGCAGGAGAT | TCTCCAAGATTCCATCCGCAG |
TNF-α | GTCCCCAAAGGGATGAGAAGTT | GTTTGCTACGACGTGGGCTACA |
IL-1β | TGTGAAATGCCACCTTTTGA | GCTCAAAGGTTTGGAAGCAG |
GAPDH | CAATGAATAGGGCTACAGCA | AGGGAGATGCTCAGTGTTGG |
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Li, H.; Wang, Y.; Yang, H.; Zhang, Y.; Xing, L.; Wang, J.; Zheng, N. Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway. Int. J. Mol. Sci. 2019, 20, 2388. https://doi.org/10.3390/ijms20102388
Li H, Wang Y, Yang H, Zhang Y, Xing L, Wang J, Zheng N. Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway. International Journal of Molecular Sciences. 2019; 20(10):2388. https://doi.org/10.3390/ijms20102388
Chicago/Turabian StyleLi, Huiying, Yizhen Wang, Huaigu Yang, Yangdong Zhang, Lei Xing, Jiaqi Wang, and Nan Zheng. 2019. "Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway" International Journal of Molecular Sciences 20, no. 10: 2388. https://doi.org/10.3390/ijms20102388