Metabolic Characterization of Cancer by Heteronuclear Multiple Quantum Coherence NMR with 13C-Labeled Glucose
| Project/Area Number |
24240071
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
Inubushi Toshiro 滋賀医科大学, 分子神経科学研究センター, 名誉教授 (20213142)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIINO Akihiko 滋賀医科大学, 分子神経科学研究センター, 准教授 (50215935)
MORIKAWA Shigehiro 滋賀医科大学, 医学部, 教授 (60220042)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥42,380,000 (Direct Cost: ¥32,600,000、Indirect Cost: ¥9,780,000)
Fiscal Year 2015: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2014: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2013: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2012: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
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| Keywords | 磁気共鳴 / グルコース代謝 / 乳酸 / ワールブルグ効果 / アルツハイマー病 / がん / NMR / グルコース / 炭素-13 / 代謝 / 多量子コヒーレンス / ｐH / 炭素ー１３ / 炭素ｰ13 / プロトンポンプ |
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| Outline of Final Research Achievements |
Aerobic glycolysis is the essential metabolic pathway for energy production in tumor cells. Gradient-enhanced heteronuclear multiple quantum coherence spectroscopy (HMQC), a kind of signal enhancement technique to truck 13C-MR tracer in vivo, was used to investigate tumor metabolism starting with 13C-labeled glucose. The detailed analysis of metabolic profile revealed that PKM2 enzyme plays pivotal role to control glycolytic flux. PKM2 inhibitor and activator suppressed lactate production and perhaps the metabolic flux bypassed to pentose phosphate pathway. Only the inhibition of lactate efflux increased the production of lactate, which indicates to modulate tumor metabolism.
We also investigated the glycolic metabolism in Alzheimer model mouse brain and found that small but definite amount of lactate signal present in any aged model mice. We concluded that lactate may play an essential role in hypometabolic brain in Alzheimer mouse model either as energy source or signaling molecule.
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Report
(5 results)
Research Products
(11 results)
