Rasić-Marković Aleksandra, Stanojlović Olivera, Hrncić Dragan, Krstić Danijela, Colović Mirjana, Susić Veselinka, Radosavljević Tatjana, Djuric Dragan
Laboratory of Neurophysiology, Institute of Medical Physiology, School of Medicine, University of Belgrade, Visegradska 26/II, 11000 Belgrade, Serbia.
Mol Cell Biochem. 2009 Jul;327(1-2):39-45. doi: 10.1007/s11010-009-0040-6. Epub 2009 Feb 18.
Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na+/K+-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of D,L-homocysteine and D,L-homocysteine thiolactone on Na+/K+- and Mg2+-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na+/K+-ATPase activity by D,L-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast, D,L-homocysteine thiolactone strongly inhibited Na+/K+-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na+/K+-ATPase and Mg2+-ATPase activities were not affected by D,L-homocysteine, while D,L-homocysteine thiolactone inhibited only Na+/K+-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na+/K+-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance.
高同型半胱氨酸血症与多种病理状况相关，包括心血管疾病、中风和认知功能障碍。向动物全身给药同型半胱氨酸可引发癫痫发作，而患有同型胱氨酸尿症的患者会出现癫痫发作。现有数据表明，同型半胱氨酸因其代谢转化为具有反应活性的硫酯——同型半胱氨酸硫内酯，可能对人体细胞有害。许多报告表明，在脑缺血、癫痫和神经退行性变中，钠钾ATP酶活性降低，这可能与兴奋性毒性机制有关。本研究的目的是检测D,L-同型半胱氨酸和D,L-同型半胱氨酸硫内酯对成年雄性大鼠红细胞、大脑皮层、海马体和脑干中钠钾ATP酶及镁ATP酶活性的体内影响。我们的结果表明，D,L-同型半胱氨酸对大鼠海马体钠钾ATP酶活性有中度抑制作用，但对大脑皮层和脑干中该酶的活性无影响。相比之下，D,L-同型半胱氨酸硫内酯强烈抑制大鼠大脑皮层、海马体和脑干中的钠钾ATP酶活性。D,L-同型半胱氨酸对红细胞钠钾ATP酶和镁ATP酶活性无影响，而D,L-同型半胱氨酸硫内酯仅抑制钠钾ATP酶活性。本研究结果表明，同型半胱氨酸硫内酯显著抑制大脑皮层、海马体和脑干中的钠钾ATP酶活性，这可能至少部分有助于理解该物质的兴奋性毒性和惊厥特性。
