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β-N-Methylamino-L-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.ORCID iD: 0000-0001-8650-6245
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Medical Product Agency, Box 26, Dag Hammarskjölds väg 42, 751 03 Uppsala, Sweden.
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2017 (English)In: Amino Acids, ISSN 0939-4451, E-ISSN 1438-2199, Vol. 49, no 5, 905-919 p.Article in journal (Refereed) Published
Abstract [en]

β-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC-MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

Place, publisher, year, edition, pages
2017. Vol. 49, no 5, 905-919 p.
Keyword [en]
BMAA, Global metabolite profiling, MS, Metabolism, NMR, Neurotoxin
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-322142DOI: 10.1007/s00726-017-2391-8ISI: 000399176200006PubMedID: 28161796OAI: oai:DiVA.org:uu-322142DiVA: diva2:1095999
Funder
Swedish Research Council Formas
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2017-05-16Bibliographically approved

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Engskog, Mikael K. R.Ersson, LisaHaglöf, JakobArvidsson, TorbjörnPettersson, CurtBrittebo, Eva
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