Department of Pharmaceutical Biosciences, Uppsala University, SE-751 24 Uppsala, Sweden; Department of Environmental Toxicology, Uppsala University, SE-752 36 Uppsala, Sweden.
Department of Analytical Chemistry, Stockholm University, SE-10691 Stockholm, Sweden.
Toxicol Lett. 2014 Apr 7;226(1):1-5. doi: 10.1016/j.toxlet.2014.01.027. Epub 2014 Jan 26.
The environmental neurotoxin β-N-methylamino-L-alanine (BMAA) is not an amino acid that is normally found in proteins. Our previous autoradiographic study of (3)H-labeled BMAA in adult mice unexpectedly revealed a tissue distribution similar to that of protein amino acids. The aim of this study was to characterize the distribution of free and protein-bound BMAA in neonatal rat tissues following a short exposure using autoradiographic imaging and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The autoradiographic imaging of (14)C-L-BMAA demonstrated a distinct uptake of radioactivity that was retained following acid extraction in tissues with a high rate of cell turnover and/or protein synthesis. The UHPLC-MS/MS analysis conclusively demonstrated a dose-dependent increase of protein-associated BMAA in neonatal rat tissues. The level of protein-associated BMAA in the liver was more than 10 times higher than that in brain regions not fully protected by the blood-brain barrier which may be due to the higher rate of protein synthesis in the liver. In conclusion, this study demonstrated that BMAA was associated with rat proteins suggesting that BMAA may be misincorporated into proteins. However, protein-associated BMAA seemed to be cleared over time, as none of the samples from adult rats had any detectable free or protein-associated BMAA.
环境神经毒素β-N-甲基氨基-L-丙氨酸（BMAA）不是一种通常存在于蛋白质中的氨基酸。我们之前对成年小鼠中（3）H 标记的 BMAA 的放射自显影研究出人意料地揭示了与蛋白质氨基酸相似的组织分布。本研究的目的是使用放射自显影成像和超高效液相色谱-串联质谱（UHPLC-MS/MS）在幼鼠组织中描述短时间暴露后游离和结合的 BMAA 的分布。（14）C-L-BMAA 的放射自显影显示，在酸提取后，具有高细胞周转率和/或蛋白质合成率的组织中保留了放射性物质的明显摄取。UHPLC-MS/MS 分析明确表明，新生大鼠组织中与蛋白质结合的 BMAA 呈剂量依赖性增加。肝中与蛋白质结合的 BMAA 水平比未完全受血脑屏障保护的脑区高 10 倍以上，这可能是由于肝脏中蛋白质合成率较高所致。总之，本研究表明 BMAA 与大鼠蛋白质结合，表明 BMAA 可能错误掺入蛋白质中。然而，随着时间的推移，与蛋白质结合的 BMAA 似乎被清除，因为成年大鼠的任何样本均未检测到游离或与蛋白质结合的 BMAA。
