A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis

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 hu...

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Autores principales:	Yoshihiro Shidoji, Chieko Iwao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Geranylgeranoic acid Lysophospholipids Hepatoma Metabolomics Cell death Biology (General) QH301-705.5 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/8a06228665d040708fb63c306070df80
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spelling	oai:doaj.org-article:8a06228665d040708fb63c306070df802021-11-26T04:35:24ZA rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis2405-580810.1016/j.bbrep.2021.101176https://doaj.org/article/8a06228665d040708fb63c306070df802021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405580821002703https://doaj.org/toc/2405-5808Geranylgeranoic 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.Yoshihiro ShidojiChieko IwaoElsevierarticleGeranylgeranoic acidLysophospholipidsHepatomaMetabolomicsCell deathBiology (General)QH301-705.5BiochemistryQD415-436ENBiochemistry and Biophysics Reports, Vol 28, Iss , Pp 101176- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Geranylgeranoic acid Lysophospholipids Hepatoma Metabolomics Cell death Biology (General) QH301-705.5 Biochemistry QD415-436
spellingShingle	Geranylgeranoic acid Lysophospholipids Hepatoma Metabolomics Cell death Biology (General) QH301-705.5 Biochemistry QD415-436 Yoshihiro Shidoji Chieko Iwao A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
description	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.
format	article
author	Yoshihiro Shidoji Chieko Iwao
author_facet	Yoshihiro Shidoji Chieko Iwao
author_sort	Yoshihiro Shidoji
title	A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
title_short	A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
title_full	A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
title_fullStr	A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
title_full_unstemmed	A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis
title_sort	rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived huh-7 cells revealed by metabolomics analysis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/8a06228665d040708fb63c306070df80
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A rapid increase in lysophospholipids after geranylgeranoic acid treatment in human hepatoma-derived HuH-7 cells revealed by metabolomics analysis

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