Comprehensive Metabolomic Analysis of IDH1 R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency.

Autor: Miyata S; Department of Neurosurgery, Jichi Medical University, Tochigi, Japan. smiyata@jichi.ac.jp., Tominaga K; Department of Biochemistry, Jichi Medical University, Tochigi, Japan. tominaga@jichi.ac.jp., Sakashita E; Department of Biochemistry, Jichi Medical University, Tochigi, Japan., Urabe M; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Onuki Y; Department of Neurosurgery, Jichi Medical University, Tochigi, Japan., Gomi A; Department of Pediatric Neurosurgery, Jichi Children's Medical Center, Jichi Medical University, Tochigi, Japan., Yamaguchi T; Department of Neurosurgery, Jichi Medical University, Tochigi, Japan., Mieno M; Department of Medical Informatics, Center for Information, Jichi Medical University, Tochigi, Japan., Mizukami H; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Kume A; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Ozawa K; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Watanabe E; Department of Neurosurgery, Jichi Medical University, Tochigi, Japan., Kawai K; Department of Neurosurgery, Jichi Medical University, Tochigi, Japan., Endo H; Department of Biochemistry, Jichi Medical University, Tochigi, Japan. hendo@jichi.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Jul 05; Vol. 9 (1), pp. 9787. Date of Electronic Publication: 2019 Jul 05.
DOI: 10.1038/s41598-019-46217-5
Abstrakt: 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.
Databáze: MEDLINE
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