A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
| Autor: | Chieko Iwao, Yoshihiro Shidoji |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
LPE
lysophosphatidylethanolamine Cell death Programmed cell death ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 LCAT lecithin cholesterol acyltransferase QH301-705.5 Short Communication D-MEM Dulbecco’s modified Eagle’s medium Biophysics ATRA all-trans retinoic acid Lysophospholipids Mevalonic acid QD415-436 KEGG Kyoto Encyclopedia of Genes and Genomes Biochemistry UPLC ultra-performance liquid chromatography chemistry.chemical_compound VIP variable importance in the projection Metabolomics FBS fetal bovine serum Q-Tof/MS quadrupole time-of-flight type mass spectrometry SPH second primary hepatoma Geranylgeranoic acid GSDMD gasdermin D Biology (General) Receptor TLR4 toll-like receptor-4 PCA principal component analysis Hepatoma LPC lysophosphatidylcholine PLA2 phospholipase A2 OPLS-DA orthogonal partial least squares-discriminant analysis Pyroptosis UPRER unfolded protein response or endoplasmic reticulum stress response LPL lysophospholipid Lysophosphatidylcholine chemistry GGA geranylgeranoic acid LPCAT LPC acyltransferase LIPC lipase C HMDB Human Metabolome Database LPA lysophosphatidic acid Intracellular |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 28, Iss, Pp 101176-(2021) Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | Geranylgeranoic acid (GGA) was developed as a preventative agent against second primary hepatoma, and was reported to induce cell death in human hepatoma cells via Toll-like receptor 4 (TLR4)-mediated pyroptosis. We recently reported that GGA is enzymatically biosynthesized from mevalonic acid in human hepatoma-derived HuH-7 cells and that endogenous GGA is found in most rat organs including the liver. An unbiased metabolomics analysis of ice-cold 50% acetonitrile extracts from control and GGA-treated cells was performed in this study to characterize the intracellular metabolic changes in GGA-induced pyroptosis and to analyze their relationship with the mechanism of GGA-induced cell death. The total positive ion chromatograms of the cellular extracts in ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were apparently unchanged after GGA treatment, but an orthogonal partial least squares-discriminant analysis score plot clearly discriminated the intracellular metabolite profiles of GGA-treated cells from that of control cells. S-plot analysis revealed 15 potential biomarkers up-regulated by 24-h GGA treatment according to their variable importance in the projection value of more than 1, and the subsequent metabolomics analysis identified nine of these metabolites as a group of lysophospholipids containing lysophosphatidylcholine with C16:0, C20:4, or C20:3 fatty acids. The possible roles of these lysophospholipids in GGA-induced pyroptosis are discussed. Highlights • Metabolomics analysis was performed on geranylgeranoic acid (GGA)-treated cells. • Total positive ion chromatograms were apparently similar after GGA treatment. • The OPLS-DA score plot distinguished the GGA-treated cells from control cells. • The S-plot analysis revealed GGA-induced upregulation of lysophospholipids. • The possible roles of lysophospholipids in GGA-induced pyroptosis are discussed. |
| Databáze: | OpenAIRE |
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