van Onselen Rianita, Kennedy Chanté, Downing Tim G
Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa; Department of Biochemistry and Microbiology, Nelson Mandela University, Gqeberha, South Africa.
Department of Biochemistry and Microbiology, Nelson Mandela University, Gqeberha, South Africa.
Environ Toxicol Pharmacol. 2024 Apr;107:104399. doi: 10.1016/j.etap.2024.104399. Epub 2024 Feb 23.
β-N-methylamino-l-alanine (BMAA) has been shown to inhibit vesicular monoamine transporter 2 (VMAT2), thereby preventing the uptake of monoaminergic neurotransmitters into platelet dense granules and synaptic vesicles. The inhibition is hypothesized to be through direct association of BMAA with hydroxyl groupꟷcontaining amino acid residues in VMAT2. This study evaluated whether BMAA-induced inhibition of VMAT2 could be prevented directly by co-incubation of BMAA with amino acids, and if this protection was specific for BMAA inhibition of VMAT2. l-tyrosine, and to a lesser extent l-serine, was able to prevent BMAA-induced VMAT2 inhibition in a concentration-dependent manner, whereas neither l-threonine nor amino acids without side chain hydroxyl groups could reduce this inhibition. Reserpine-induced VMAT2 inhibition was unaffected by any of the amino acids. These data support the hypothesized interaction between BMAA and hydroxyl groupꟷcontaining amino acids and suggests that this interaction might be leveraged to protect against the toxicity of BMAA.
β-N-甲基氨基-L-丙氨酸（BMAA）已被证明可抑制囊泡单胺转运体2（VMAT2），从而阻止单胺能神经递质摄取到血小板致密颗粒和突触小泡中。据推测，这种抑制作用是通过BMAA与VMAT2中含羟基的氨基酸残基直接结合实现的。本研究评估了BMAA与氨基酸共同孵育是否能直接预防BMAA诱导的VMAT2抑制，以及这种保护作用是否对BMAA抑制VMAT2具有特异性。L-酪氨酸以及程度稍低的L-丝氨酸能够以浓度依赖的方式预防BMAA诱导的VMAT2抑制，而L-苏氨酸和没有侧链羟基的氨基酸均不能降低这种抑制作用。利血平诱导的VMAT2抑制不受任何一种氨基酸的影响。这些数据支持了BMAA与含羟基氨基酸之间的推测性相互作用，并表明这种相互作用可能有助于预防BMAA的毒性。
