Potential transfer of neurotoxic amino acid β-N-methylamino-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines.
β-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.
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden.
Marie
M
Andersson
Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden.
Lisa
L
Ersson
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden. Electronic address: Ingvar.Brandt@ebc.uu.se.
Ingvar
I
Brandt
Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden; Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-164 90 Stockholm, Sweden.
Ulrika
U
Bergström
D000599:Amino Acids, Diamino / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001942:Breast Feeding / Q000009:adverse effects*; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D005544:Forecasting; D006801:Humans; D007231:Infant, Newborn; D007774:Lactation / Q000187:drug effects / Q000378:metabolism*; D061986:MCF-7 Cells; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D009035:Mothers
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D018690:Excitatory Amino Acid Agonists; C001824:beta-N-methylamino-L-alanine
Amino acid transporters; BMAA; Breast milk; Cellular transport; Neurodegeneration