title: Cerebral uptake and protein incorporation of cyanobacterial toxin β-N-methylamino-L-alanine.
abstract: β-N-methylamino-L-alanine (BMAA) is a nonprotein amino acid produced by diverse species of free-living cyanobacteria found in terrestrial and aquatic environments worldwide. BMAA has been detected as a soluble (free) and insoluble protein-bound (bound) amino acid in brains of Alzheimer's disease, amyotrophic lateral sclerosis, and Guamanian amyotrophic lateral sclerosis/Parkinsonism dementia complex patients. A toxic reservoir of BMAA in the brain may be excitotoxic to neurons or serve to disrupt cerebral protein homeostasis. Here, we report tracer uptake kinetics and a time course for protein incorporation of [C]-L-BMAA into the brain of C57/BL6 mice. BMAA pharmacokinetic parameters measured in plasma show a rapid distribution phase and a terminal elimination half-life of 1.7 days following bolus intravenous administration. Total [C]-L-BMAA uptake to the brain reached a maximum at 1.5 h. Ex-vivo autoradiography of [C]-labeled BMAA showed dense labeling within the ventricles, choroid plexus, and whole-brain gray matter structures. Radioactivity measured in soluble and trichloroacetic acid precipitates was compared to determine the incorporation of [C]-L-BMAA into total brain protein. The maximal concentration of [C]-L-BMAA was measured in protein-bound fractions of brain at 4 h, followed by a corresponding decrease in the free pool of this nonprotein amino acid. The time-dependent association of [C]-L-BMAA in the protein-bound fraction suggests that BMAA may be trapped in new proteins by protein synthesis-dependent processes. BMAA may accumulate into growing polypeptide chains and recycle to the free pool with protein turnover.
authors: Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
authors: Xiaobin
authors: X
authors: Xie
authors: Margaret
authors: M
authors: Basile
authors: Deborah C
authors: DC
authors: Mash
mesh_terms: D000599:Amino Acids, Diamino / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D003704:Dementia / Q000378:metabolism; D004195:Disease Models, Animal; D006207:Half-Life; D008387:Marine Toxins / Q000378:metabolism*; D051379:Mice; D052998:Microcystins / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*
chemical_list: D000599:Amino Acids, Diamino; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine