4.7 Article

Comprehensive Metabolomic Analysis of IDH1R132H Clinical Glioma Samples Reveals Suppression of β-oxidation Due to Carnitine Deficiency

Journal

SCIENTIFIC REPORTS
Volume 9, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-46217-5

Keywords

-

Funding

  1. FY2012 Jichi Medical School Research Encouragement Award
  2. MEXT-Supported Program for the Strategic Research Foundation at Private Universities 2013-2017
  3. Japan Society for the Promotion of Sciences [17K16659, 17K08497, 17K11248]
  4. FY2011 Grand Prize for Promotion of Human Metabolome Technologies Metabolomics Cutting Edge Research
  5. Grants-in-Aid for Scientific Research [17K11248, 17K08497, 17K16659] Funding Source: KAKEN

Ask authors/readers for more resources

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 beta-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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemistry & Molecular Biology

Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid

Ryota Watano, Tsukasa Ohmori, Shuji Hishikawa, Asuka Sakata, Hiroaki Mizukami

GENE THERAPY (2020)

Article Neurosciences

Axonal Projections from Middle Temporal Area to the Pulvinar in the Common Marmoset

Akira Arafune-Mishima, Hiroshi Abe, Toshiki Tani, Hiromi Mashiko, Satoshi Watanabe, Kazuhisa Sakai, Wataru Suzuki, Hiroaki Mizukami, Akiya Watakabe, Tetsuo Yamamori, Noritaka Ichinohe

NEUROSCIENCE (2020)

Article Multidisciplinary Sciences

Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models

Machi Horiai, Ayano Otsuka, Shizu Hidema, Yuichi Hiraoka, Ryotaro Hayashi, Shinji Miyazaki, Tamio Furuse, Hiroaki Mizukami, Ryoichi Teruyama, Masaru Tamura, Haruhiko Bito, Yuko Maejima, Kenju Shimomura, Katsuhiko Nishimori

SCIENTIFIC REPORTS (2020)

Article Oncology

Knockout of vasohibin-2 reduces tubulin carboxypeptidase activity and increases paclitaxel sensitivity in ovarian cancer

Takahiro Koyanagi, Yasushi Saga, Yoshifumi Takahashi, Kohei Tamura, Takahiro Yoshiba, Suzuyo Takahashi, Akiyo Taneichi, Yuji Takei, Masashi Urabe, Hiroaki Mizukami, Hiroyuki Fujiwara

Summary: VASH2 knockout in ovarian cancer cells enhances chemosensitivity to paclitaxel by reducing tubulin detyrosination and upregulating cyclin B1 expression. This study suggests that targeting VASH2 may be a promising strategy for ovarian cancer treatment by inhibiting angiogenesis and modulating microtubule activity.

CANCER MEDICINE (2021)

Article Biochemistry & Molecular Biology

Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage

Mari Isomi, Taketaro Sadahiro, Ryo Fujita, Yuto Abe, Yu Yamada, Tatsuya Akiyama, Hiroaki Mizukami, Tsugumine Shu, Keiichi Fukuda, Masaki Ieda

Summary: Adult hearts have limited regenerative capacity, but direct reprogramming of cardiac fibroblasts into induced cardiomyocytes with GMT may have significant potential for cardiac repair. Studies have shown that SeV-GMT reprogramming in mouse hearts after acute MI can improve cardiac function.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

Letter Cardiac & Cardiovascular Systems

Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart

Mari Isomi, Taketaro Sadahiro, Hiroyuki Yamakawa, Ryo Fujita, Yu Yamada, Yuto Abe, Yoshiko Murakata, Tatsuya Akiyama, Tsugumine Shu, Hiroaki Mizukami, Keiichi Fukuda, Masaki Ieda

CIRCULATION (2021)

Article Biotechnology & Applied Microbiology

Higher Transduction Efficiency of AAV5 to Neural Stem Cells and Immature Neurons in Gerbil Dentate Gyrus Compared to AAV2 and rh10

Yoshihide Sehara, Yuka Hayashi, Kenji Ohba, Ryosuke Uchibori, Masashi Urabe, Ayumu Inutsuka, Kuniko Shimazaki, Kensuke Kawai, Hiroaki Mizukami

Summary: This study compared the transduction efficiency of AAV2, 5, and rh10 in the hippocampal DG, finding that AAV5 exhibited a higher efficiency in neural stem cells and precursor cells, while AAVrh10 showed a greater efficiency in mature neurons.

HUMAN GENE THERAPY (2022)

Article Endocrinology & Metabolism

Roles of fibroblast growth factor 21 in the control of depression-like behaviours after social defeat stress in male rodents

Naoki Usui, Masahide Yoshida, Yuki Takayanagi, Naranbat Nasanbuyan, Ayumu Inutsuka, Hiroshi Kurosu, Hiroaki Mizukami, Yoshiyuki Mori, Makoto Kuro-o, Tatsushi Onaka

Summary: FGF21 plays a role in modulating energy metabolism, neuroendocrine stress responses, and controlling behavioral changes in male rodents under social defeat stress conditions. The study suggests that endogenous FGF21 may have an inhibitory effect on stress-induced depression-like behavior in male rodents.

JOURNAL OF NEUROENDOCRINOLOGY (2021)

Article Multidisciplinary Sciences

Loss of mitochondrial transcription factor A in neural stem cells leads to immature brain development and triggers the activation of the integral stress response in vivo

Rintaro Kuroda, Kaoru Tominaga, Katsumi Kasashima, Kenji Kuroiwa, Eiji Sakashita, Hiroko Hayakawa, Tom Kouki, Nobuhiko Ohno, Kensuke Kawai, Hitoshi Endo

Summary: Mitochondrial dysfunction caused by Tfam inactivation in neural stem cells impairs respiratory chain activities, leading to deficits in neural differentiation and maturation in both in vivo and in vitro settings. This dysfunction triggers an integrated stress response that may protect against neurodegenerative diseases.

PLOS ONE (2021)

Article Immunology

Liver-Directed AAV8 Booster Vaccine Expressing Plasmodium falciparumYY Antigen Following Adenovirus Vaccine Priming Elicits Sterile Protection in a Murine Model

Mohammad Shahnaij, Mitsuhiro Iyori, Hiroaki Mizukami, Mayu Kajino, Iroha Yamagoshi, Intan Syafira, Yenni Yusuf, Ken Fujiwara, Daisuke S. Yamamoto, Hirotomo Kato, Nobuhiko Ohno, Shigeto Yoshida

Summary: By using AAV8 as a booster, the immune responses in mice were improved, providing better protection against malaria and demonstrating great promise as a next-generation platform for effective malaria vaccine development.

FRONTIERS IN IMMUNOLOGY (2021)

Article Medicine, Research & Experimental

A sensitive and reproducible cell-based assay via secNanoLuc to detect neutralizing antibody against adeno-associated virus vector capsid

Nemekhbayar Baatartsogt, Yuji Kashiwakura, Morisada Hayakawa, Nobuhiko Kamoshita, Takafumi Hiramoto, Hiroaki Mizukami, Tsukasa Ohmori

Summary: A reliable and sensitive cell-based assay to measure neutralizing antibodies against AAV was developed with a detection threshold of 100. High-dose AAV8 vector treatment enabled evasion of the inhibitory effect of neutralizing antibodies, while low-dose treatment may have slight influence even when antibodies are negative in the assay.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2021)

Article Biochemistry & Molecular Biology

Dark Rearing in the Visual Critical Period Causes Structural Changes in Myelinated Axons in the Adult Mouse Visual Pathway

Yasuyuki Osanai, Batpurev Battulga, Reiji Yamazaki, Tom Kouki, Megumi Yatabe, Hiroaki Mizukami, Kenta Kobayashi, Yoshiaki Shinohara, Yumiko Yoshimura, Nobuhiko Ohno

Summary: An appropriate sensory experience during the early developmental period is crucial for brain maturation. Dark rearing during the visual critical period affects the structure and morphology of myelin sheaths in the visual pathway, resulting in thicker and shorter sheaths.

NEUROCHEMICAL RESEARCH (2022)

Article Biochemistry & Molecular Biology

Tip60/KAT5 Histone Acetyltransferase Is Required for Maintenance and Neurogenesis of Embryonic Neural Stem Cells

Kaoru Tominaga, Eiji Sakashita, Katsumi Kasashima, Kenji Kuroiwa, Yasumitsu Nagao, Naoki Iwamori, Hitoshi Endo

Summary: Epigenetic factors play a crucial role in establishing functional organ systems during development, including brain development. However, the precise mechanism of epigenetic regulation in brain development and neurogenesis remains largely unknown. In this study, the researchers discovered the critical role of the Tip60 protein in brain development and the maintenance and function of neural stem/progenitor cells (NSCs). Tip60 deficiency led to multiple abnormalities in brain development, including microcephaly, reduced proliferation of developing brain cells, and impaired neural differentiation and migration. The study also revealed that Tip60 is involved in the transition from neurogenesis to gliogenesis during brain development.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Neurosciences

Inversed Effects of Nav1.2 Deficiency at Medial Prefrontal Cortex and Ventral Tegmental Area for Prepulse Inhibition in Acoustic Startle Response

Toshimitsu Suzuki, Satoko Hattori, Hiroaki Mizukami, Ryuichi Nakajima, Yurina Hibi, Saho Kato, Mahoro Matsuzaki, Ryu Ikebe, Tsuyoshi Miyakawa, Kazuhiro Yamakawa

Summary: This study found that deletion of the Scn2a gene in schizophrenia-related brain regions (medial prefrontal cortex and ventral tegmental area) in mice resulted in schizophrenia-relevant behavioral abnormalities. These findings are important for understanding the pathological mechanisms of schizophrenia.

MOLECULAR NEUROBIOLOGY (2023)

Meeting Abstract Biotechnology & Applied Microbiology

Intra-Cisterna Magna Injection of an AAV Vector with the GLUT1 Promoter Transduces Endothelial Cells and Neurons in Broad Areas of Pig Brain without Toxicity

Sachie Nakamura, Hitoshi Osaka, Shin-ichi Muramatsu, Naomi Takino, Mika Ito, Eriko F. Jimbo, Hiroaki Mizukami, Shuji Hishikawa, Takeshi Nakajima, Takanori Yamagata

MOLECULAR THERAPY (2020)

No Data Available