A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis |
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| Authors: | Yoshihiro Shidoji Chieko Iwao |
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| Affiliation: | Molecular and Cellular Biology, Graduate School of Human Health Science, University of Nagasaki, Nagayo, Nagasaki, 851-2195, Japan |
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| Abstract: | 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. |
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| Keywords: | Geranylgeranoic acid Lysophospholipids Hepatoma Metabolomics Cell death ATRA" },{" #name" :" keyword" ," $" :{" id" :" pc_p6Zqhx1F5y" }," $$" :[{" #name" :" text" ," $$" :[{" #name" :" __text__" ," _" :" all-" },{" #name" :" italic" ," _" :" trans" },{" #name" :" __text__" ," _" :" retinoic acid D-MEM" },{" #name" :" keyword" ," $" :{" id" :" pc_uYjCeec00J" }," $$" :[{" #name" :" text" ," _" :" Dulbecco’s modified Eagle’s medium ENPP2" },{" #name" :" keyword" ," $" :{" id" :" pc_giZNJtFj74" }," $$" :[{" #name" :" text" ," _" :" ectonucleotide pyrophosphatase/phosphodiesterase 2 FBS" },{" #name" :" keyword" ," $" :{" id" :" pc_AmPfsq4sKO" }," $$" :[{" #name" :" text" ," _" :" fetal bovine serum GGA" },{" #name" :" keyword" ," $" :{" id" :" pc_o0pttb1neB" }," $$" :[{" #name" :" text" ," _" :" geranylgeranoic acid GSDMD" },{" #name" :" keyword" ," $" :{" id" :" pc_KRuBbk1UI8" }," $$" :[{" #name" :" text" ," _" :" gasdermin D HMDB" },{" #name" :" keyword" ," $" :{" id" :" pc_b9nngcnXBJ" }," $$" :[{" #name" :" text" ," _" :" Human Metabolome Database KEGG" },{" #name" :" keyword" ," $" :{" id" :" pc_OwlfWtIPrQ" }," $$" :[{" #name" :" text" ," _" :" Kyoto Encyclopedia of Genes and Genomes LCAT" },{" #name" :" keyword" ," $" :{" id" :" pc_VEFQVUYnYg" }," $$" :[{" #name" :" text" ," _" :" lecithin cholesterol acyltransferase LIPC" },{" #name" :" keyword" ," $" :{" id" :" pc_giHyHIwTd1" }," $$" :[{" #name" :" text" ," _" :" lipase C LPA" },{" #name" :" keyword" ," $" :{" id" :" pc_2rLdsrvCoR" }," $$" :[{" #name" :" text" ," _" :" lysophosphatidic acid LPC" },{" #name" :" keyword" ," $" :{" id" :" pc_V28EJYuBDS" }," $$" :[{" #name" :" text" ," _" :" lysophosphatidylcholine LPCAT" },{" #name" :" keyword" ," $" :{" id" :" pc_U9PxJggQlY" }," $$" :[{" #name" :" text" ," _" :" LPC acyltransferase LPE" },{" #name" :" keyword" ," $" :{" id" :" pc_jqJLwBU4rK" }," $$" :[{" #name" :" text" ," _" :" lysophosphatidylethanolamine LPL" },{" #name" :" keyword" ," $" :{" id" :" pc_gd8RixT8pD" }," $$" :[{" #name" :" text" ," _" :" lysophospholipid OPLS-DA" },{" #name" :" keyword" ," $" :{" id" :" pc_d4CdMwYSK4" }," $$" :[{" #name" :" text" ," _" :" orthogonal partial least squares-discriminant analysis PCA" },{" #name" :" keyword" ," $" :{" id" :" pc_yECRwvnPgl" }," $$" :[{" #name" :" text" ," _" :" principal component analysis PLA2" },{" #name" :" keyword" ," $" :{" id" :" pc_gcBONQRjOu" }," $$" :[{" #name" :" text" ," _" :" phospholipase A2 Q-Tof/MS" },{" #name" :" keyword" ," $" :{" id" :" pc_c8HBfCbRE2" }," $$" :[{" #name" :" text" ," _" :" quadrupole time-of-flight type mass spectrometry SPH" },{" #name" :" keyword" ," $" :{" id" :" pc_RlQRJduxFo" }," $$" :[{" #name" :" text" ," _" :" second primary hepatoma TLR4" },{" #name" :" keyword" ," $" :{" id" :" pc_5o4vPXdiwF" }," $$" :[{" #name" :" text" ," _" :" toll-like receptor-4 UPLC" },{" #name" :" keyword" ," $" :{" id" :" pc_sZnMhhspUb" }," $$" :[{" #name" :" text" ," _" :" ultra-performance liquid chromatography unfolded protein response or endoplasmic reticulum stress response VIP" },{" #name" :" keyword" ," $" :{" id" :" pc_VgH8jOgt1A" }," $$" :[{" #name" :" text" ," _" :" variable importance in the projection |
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