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Toxins 2017, 9(12), 400;

Investigating β-N-Methylamino-l-alanine Misincorporation in Human Cell Cultures: A Comparative Study with Known Amino Acid Analogues

Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa
Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa
Authors to whom correspondence should be addressed.
Academic Editor: Amparo Alfonso
Received: 30 November 2017 / Revised: 12 December 2017 / Accepted: 13 December 2017 / Published: 14 December 2017
(This article belongs to the Special Issue The Cyanobacterial Neurotoxin BMAA)
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Misincorporation of β-N-methylamino-l-alanine (BMAA) into proteins has been proposed to be a mechanism of toxicity to explain the role of BMAA in neurodegenerative disease development. However, studies have shown that all detectable BMAA can be removed from proteins by SDS-PAGE purification and that the toxicity of l-canavanine cannot be reproduced in prokaryotes or in a rat pheochromocytoma cell line, strongly indicating that the misincorporation hypothesis of BMAA should be re-investigated. The aim of this study was therefore to determine if BMAA misincorporates into proteins in cells of human origin with subsequent misincorporation-type toxicity. Almost complete loss of viability in response to exposure to l-4-fluorophenylalanine and l-m-tyrosine was observed in all of the cell lines, corresponding to a concentration-dependent increase of the analogues in protein extracts from exposed cells. In contrast, BMAA exposure resulted in slight toxicity in one of the cell lines but the observed toxicity was not the result of misincorporation of BMAA into proteins, as no BMAA was detected in any of the SDS-PAGE purified protein extracts that were obtained from the cells following BMAA exposure. The results show that BMAA is not misincorporated into human proteins and that misincorporation is not a valid mechanism of toxicity. View Full-Text
Keywords: β-N-methylamino-l-alanine; BMAA; misincorporation; analogues; m-tyrosine; l-4-fluorophenylalanine β-N-methylamino-l-alanine; BMAA; misincorporation; analogues; m-tyrosine; l-4-fluorophenylalanine

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Onselen, R.V.; Downing, S.; Kemp, G.; Downing, T. Investigating β-N-Methylamino-l-alanine Misincorporation in Human Cell Cultures: A Comparative Study with Known Amino Acid Analogues. Toxins 2017, 9, 400.

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