Capiotti Katiucia Marques, Fazenda Lidiane, Nazario Luiza Reali, Menezes Fabiano Peres, Kist Luiza Wilges, Bogo Maurício Reis, Da Silva Rosane Souza, Wyse Angela Terezinha, Bonan Carla Denise
Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2013 Feb;31(1):75-81. doi: 10.1016/j.ijdevneu.2012.09.002. Epub 2012 Sep 17.
Hyperargininemia is an inborn error of metabolism (IEM) characterized by tissue accumulation of arginine (Arg). Mental retardation and other neurological features are common symptoms in hyperargininemic patients. Considering purinergic signaling has a crucial role from the early stages of development and underlying mechanisms of this disease are poorly established, we investigated the effect of Arg administration on locomotor activity, morphological alterations, and extracellular nucleotide hydrolysis in larvae and adult zebrafish. We showed that 0.1 mM Arg was unable to promote changes in locomotor activity. In addition, 7-day-post-fertilization (dpf) larvae treated with Arg demonstrated a decreased body size. Arg exposure (0.1 mM) promoted an increase in ATP, ADP, and AMP hydrolysis when compared to control group. These findings demonstrated that Arg might affect morphological parameters and ectonucleotidase activities in zebrafish larvae, suggesting that purinergic system is a target for neurotoxic effects induced by Arg.
高精氨酸血症是一种先天性代谢缺陷病（IEM），其特征是精氨酸（Arg）在组织中蓄积。智力发育迟缓及其他神经学特征是高精氨酸血症患者的常见症状。鉴于嘌呤能信号在发育早期起关键作用，且该疾病的潜在机制尚不明确，我们研究了精氨酸给药对斑马鱼幼体和成体的运动活性、形态改变及细胞外核苷酸水解的影响。我们发现，0.1 mM的精氨酸无法促进运动活性的改变。此外，用精氨酸处理的受精后7天（dpf）幼体体型减小。与对照组相比，暴露于精氨酸（0.1 mM）会促进ATP、ADP和AMP水解增加。这些发现表明，精氨酸可能会影响斑马鱼幼体的形态参数和外核苷酸酶活性，提示嘌呤能系统是精氨酸诱导神经毒性作用的靶点。
