Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency
Abstract Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To unde...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2019
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5f6a67cbdf8045f0aa03230bb5c89474 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5f6a67cbdf8045f0aa03230bb5c89474 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5f6a67cbdf8045f0aa03230bb5c894742021-12-02T15:09:49ZComprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency10.1038/s41598-019-46217-52045-2322https://doaj.org/article/5f6a67cbdf8045f0aa03230bb5c894742019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46217-5https://doaj.org/toc/2045-2322Abstract Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II–IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1 R132H . In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas.Satsuki MiyataKaoru TominagaEiji SakashitaMasashi UrabeYoshiyuki OnukiAkira GomiTakashi YamaguchiMakiko MienoHiroaki MizukamiAkihiro KumeKeiya OzawaEiju WatanabeKensuke KawaiHitoshi EndoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Satsuki Miyata Kaoru Tominaga Eiji Sakashita Masashi Urabe Yoshiyuki Onuki Akira Gomi Takashi Yamaguchi Makiko Mieno Hiroaki Mizukami Akihiro Kume Keiya Ozawa Eiju Watanabe Kensuke Kawai Hitoshi Endo Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency |
| description |
Abstract Gliomas with Isocitrate dehydrogenase 1 (IDH1) mutation have alterations in several enzyme activities, resulting in various metabolic changes. The aim of this study was to determine a mechanism for the better prognosis of gliomas with IDH mutation by performing metabolomic analysis. To understand the metabolic state of human gliomas, we analyzed clinical samples obtained from surgical resection of glioma patients (grades II–IV) with or without the IDH1 mutation, and compared the results with U87 glioblastoma cells overexpressing IDH1 or IDH1 R132H . In clinical samples of gliomas with IDH1 mutation, levels of D-2-hydroxyglutarate (D-2HG) were increased significantly compared with gliomas without IDH mutation. Gliomas with IDH mutation also showed decreased intermediates in the tricarboxylic acid cycle and pathways involved in the production of energy, amino acids, and nucleic acids. The marked difference in the metabolic profile in IDH mutant clinical glioma samples compared with that of mutant IDH expressing cells includes a decrease in β-oxidation due to acyl-carnitine and carnitine deficiencies. These metabolic changes may explain the lower cell division rate observed in IDH mutant gliomas and may provide a better prognosis in IDH mutant gliomas. |
| format |
article |
| author |
Satsuki Miyata Kaoru Tominaga Eiji Sakashita Masashi Urabe Yoshiyuki Onuki Akira Gomi Takashi Yamaguchi Makiko Mieno Hiroaki Mizukami Akihiro Kume Keiya Ozawa Eiju Watanabe Kensuke Kawai Hitoshi Endo |
| author_facet |
Satsuki Miyata Kaoru Tominaga Eiji Sakashita Masashi Urabe Yoshiyuki Onuki Akira Gomi Takashi Yamaguchi Makiko Mieno Hiroaki Mizukami Akihiro Kume Keiya Ozawa Eiju Watanabe Kensuke Kawai Hitoshi Endo |
| author_sort |
Satsuki Miyata |
| title |
Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency |
| title_short |
Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency |
| title_full |
Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency |
| title_fullStr |
Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency |
| title_full_unstemmed |
Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency |
| title_sort |
comprehensive metabolomic analysis of idh1 r132h clinical glioma samples reveals suppression of β-oxidation due to carnitine deficiency |
| publisher |
Nature Portfolio |
| publishDate |
2019 |
| url |
https://doaj.org/article/5f6a67cbdf8045f0aa03230bb5c89474 |
| work_keys_str_mv |
AT satsukimiyata comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT kaorutominaga comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT eijisakashita comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT masashiurabe comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT yoshiyukionuki comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT akiragomi comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT takashiyamaguchi comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT makikomieno comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT hiroakimizukami comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT akihirokume comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT keiyaozawa comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT eijuwatanabe comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT kensukekawai comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency AT hitoshiendo comprehensivemetabolomicanalysisofidh1r132hclinicalgliomasamplesrevealssuppressionofboxidationduetocarnitinedeficiency |
| _version_ |
1718387753643671552 |