Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Toxicol Appl Pharmacol ; 320: 40-50, 2017 04 01.
Article in English | MEDLINE | ID: mdl-28174119

ABSTRACT

ß-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.


Subject(s)
Amino Acids, Diamino/metabolism , Breast Feeding/adverse effects , Excitatory Amino Acid Agonists/metabolism , Lactation/metabolism , Maternal Exposure/adverse effects , Amino Acids, Diamino/toxicity , Animals , Biological Transport/drug effects , Biological Transport/physiology , Caco-2 Cells , Cell Differentiation/drug effects , Cell Differentiation/physiology , Cell Line , Cyanobacteria Toxins , Dose-Response Relationship, Drug , Excitatory Amino Acid Agonists/toxicity , Female , Forecasting , Humans , Infant, Newborn , Lactation/drug effects , MCF-7 Cells , Mice , Mothers
2.
Amino Acids ; 49(5): 905-919, 2017 05.
Article in English | MEDLINE | ID: mdl-28161796

ABSTRACT

ß-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.


Subject(s)
Alanine/metabolism , Amino Acids, Diamino/toxicity , Aspartic Acid/metabolism , Cytotoxins/toxicity , Glutamic Acid/metabolism , Neurons/drug effects , Cell Differentiation/drug effects , Cell Line, Tumor , Cyanobacteria Toxins , Dose-Response Relationship, Drug , Humans , Metabolic Networks and Pathways/drug effects , Metabolome , Neurons/cytology , Neurons/metabolism , Principal Component Analysis , Taurine/metabolism , Tretinoin/pharmacology , gamma-Aminobutyric Acid/metabolism
3.
Sci Rep ; 5: 15570, 2015 Oct 26.
Article in English | MEDLINE | ID: mdl-26498001

ABSTRACT

ß-Methylamino-L-alanine (BMAA) is implicated in the aetiology of neurodegenerative disorders. Neonatal exposure to BMAA induces cognitive impairments and progressive neurodegenerative changes including intracellular fibril formation in the hippocampus of adult rats. It is unclear why the neonatal hippocampus is especially vulnerable and the critical cellular perturbations preceding BMAA-induced toxicity remains to be elucidated. The aim of this study was to compare the level of free and protein-associated BMAA in neonatal rat brain and peripheral tissues after different exposures to BMAA. Ultra-high performance liquid chromatography-tandem mass spectrometry analysis revealed that BMAA passed the neonatal blood-brain barrier and was distributed to all studied brain areas. BMAA was also associated to proteins in the brain, especially in the hippocampus. The level in the brain was, however, considerably lower compared to the liver that is not a target organ for BMAA. In contrast to the liver there was a significantly increased level of protein-association of BMAA in the hippocampus and other brain areas following repeated administration suggesting that the degradation of BMAA-associated proteins may be lower in neonatal brain than in the liver. Additional evidence is needed in support of a role for protein misincorporation in the neonatal hippocampus for long-term effects of BMAA.


Subject(s)
Amino Acids, Diamino/pharmacokinetics , Hippocampus/metabolism , Amino Acids, Diamino/toxicity , Animals , Animals, Newborn , Blood-Brain Barrier , Chromatography, Liquid , Cognition Disorders/chemically induced , Cyanobacteria Toxins , Hippocampus/drug effects , Hippocampus/growth & development , Liver/metabolism , Male , Mass Spectrometry , Proteins/metabolism , Rats , Rats, Wistar
SELECTION OF CITATIONS
SEARCH DETAIL
...