In Vivo Assessment of Increased Oxidation of Branched-Chain Amino Acids in Glioblastoma

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dc.contributor.ORCID0000-0002-7404-6971 (Park, JM)
dc.contributor.ORCID0000-0001-7150-8301 (Sherry, AD)
dc.contributor.authorSuh, Eul Hyun
dc.contributor.authorHackett, Edward P.
dc.contributor.authorWynn, R. Max
dc.contributor.authorChuang, David T.
dc.contributor.authorZhang, Bo
dc.contributor.authorLuo, Weibo
dc.contributor.authorSherry, A. Dean
dc.contributor.authorPark, Jae Mo
dc.contributor.utdAuthorSherry, A. Dean
dc.contributor.utdAuthorPark, Jae Mo
dc.date.accessioned2020-12-17T16:58:20Z
dc.date.available2020-12-17T16:58:20Z
dc.date.issued2019-01-23
dc.descriptionIncludes supplementary material
dc.description.abstractAltered branched-chain amino acids (BCAAs) metabolism is a distinctive feature of various cancers and plays an important role in sustaining tumor proliferation and aggressiveness. Despite the therapeutic and diagnostic potentials, the role of BCAA metabolism in cancer and the activities of associated enzymes remain unclear. Due to its pivotal role in BCAA metabolism and rapid cellular transport, hyperpolarized ¹³C-labeled α-ketoisocaproate (KIC), the α-keto acid corresponding to leucine, can assess both BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase complex (BCKDC) activities via production of [1-¹³C]leucine or ¹³CO₂ (and thus (H¹³CO₃-), respectively. Here, we investigated BCAA metabolism of F98 rat glioma model in vivo using hyperpolarized ¹³C-KIC. In tumor regions, we observed a decrease in ¹³C-leucine production from injected hyperpolarized ¹³C-KIC via BCAT compared to the contralateral normal-appearing brain, and an increase in H¹³CO₃-, a catabolic product of KIC through the mitochondrial BCKDC. A parallel ex vivo ¹³C NMR isotopomer analysis following steady-state infusion of [U-¹³C] leucine to glioma-bearing rats verified the increased oxidation of leucine in glioma tissue. Both the in vivo hyperpolarized KIC imaging and the leucine infusion study indicate that KIC catabolism is upregulated through BCAT/BCKDC and further oxidized via the citric acid cycle in F98 glioma.
dc.description.departmentErik Jonsson School of Engineering and Computer Science
dc.description.departmentSchool of Natural Sciences and Mathematics
dc.identifier.bibliographicCitationSuh, Eul Hyun, Edward P. Hackett, R. Max Wynn, David T. Chuang, et al. 2019. "In vivo assessment of increased oxidation of branched-chain amino acids in glioblastoma." Scientific Reports 9: art. 340, doi: 10.1038/s41598-018-37390-0
dc.identifier.issn2045-2322
dc.identifier.urihttps://dx.doi.org/10.1038/s41598-018-37390-0
dc.identifier.urihttps://hdl.handle.net/10735.1/9106
dc.identifier.volume9
dc.language.isoen
dc.publisherNature Publishing Group
dc.rightsCC BY 4.0 (Attribution)
dc.rights©2019 The Authors
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.source.journalScientific Reports
dc.subjectCell proliferation
dc.subjectBreast--Cancer
dc.subjectMetabolism
dc.subjectGene expression
dc.subjectGliomas
dc.subjectAminotransferases
dc.subjectAcetates
dc.subjectBiochemical markers
dc.subject.meshBCAT1 protein, human
dc.subject.meshBreast Neoplasms
dc.titleIn Vivo Assessment of Increased Oxidation of Branched-Chain Amino Acids in Glioblastoma
dc.type.genrearticle

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Park, Jae Mo
Sherry, A. Dean