Blood-Brain Interactions Group, School of Psychology & Psychiatry, Monash University, Clayton, VIC 3800, Australia.
Free Radic Biol Med. 2010 Aug 15;49(4):649-57. doi: 10.1016/j.freeradbiomed.2010.05.023. Epub 2010 Jun 4.
In epilepsy, traumatic brain injury, and ischemic stroke, toxic levels of zinc released from neurons contribute to the brain damage associated with these disorders. Zinc causes oxidative stress by increasing the generation of reactive oxygen species and by inhibiting glutathione reductase (GR). This study investigated whether naturally occurring amino acids can protect cultured mouse astrocytes from zinc. Astrocytes incubated for 24h with 33 microM zinc acetate in a minimal medium displayed a loss of GR activity, a depletion of total glutathione, and a loss of total antioxidant capacity. These changes were accompanied by extensive cell death. Four amino acids (200 microM L-histidine, 201 microM L-cystine, 4mM L-glutamine, 798 microM L-threonine), which are a subset of the 15 present in Dulbecco's modified Eagle medium, were found to collectively prevent zinc toxicity. Histidine was the most protective, followed by cystine, glutamine, and threonine. It is proposed that each of these amino acids protects against different aspects of zinc toxicity by chelating zinc, by serving as precursors for glutathione, or by converting to tricarboxylic acid cycle intermediates. It is possible that these 4 amino acids contribute in vivo to the protection of brain cells from the toxic effects of zinc.
在癫痫、创伤性脑损伤和缺血性中风中，神经元释放的毒性水平锌导致与这些疾病相关的脑损伤。锌通过增加活性氧的生成和抑制谷胱甘肽还原酶（GR）来引起氧化应激。本研究调查了天然存在的氨基酸是否可以保护培养的小鼠星形胶质细胞免受锌的侵害。在最小培养基中用 33μM 醋酸锌孵育 24 小时的星形胶质细胞显示出 GR 活性丧失、总谷胱甘肽耗竭以及总抗氧化能力丧失。这些变化伴随着广泛的细胞死亡。发现四种氨基酸（200μM L-组氨酸、201μM L-半胱氨酸、4mM L-谷氨酰胺、798μM L-苏氨酸），它们是杜氏改良 Eagle 培养基中存在的 15 种氨基酸的一部分，可以共同预防锌毒性。组氨酸的保护作用最强，其次是半胱氨酸、谷氨酰胺和苏氨酸。据推测，这些氨基酸中的每一种都通过螯合锌、作为谷胱甘肽的前体或转化为三羧酸循环中间产物来防止锌毒性的不同方面。这四种氨基酸可能在体内有助于保护脑细胞免受锌的毒性影响。
