Stefanello Francieli M, Chiarani Fábria, Kurek Andréa G, Wannmacher Clovis M D, Wajner Moacir, Wyse Angela T S
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2005 Nov;23(7):651-6. doi: 10.1016/j.ijdevneu.2005.06.003. Epub 2005 Aug 10.
In the present study we investigated the effect of methionine exposure of hippocampus homogenates on Na+,K+-ATPase activity from synaptic plasma membrane of rats. Results showed that methionine significantly decreased this enzyme activity. We also evaluated the effect of incubating glutathione (GSH) and trolox (alpha-tocopherol) alone or combined with methionine on Na+,K+-ATPase activity. The tested antioxidants per se did not alter the enzymatic activity, but prevented the inhibitory action of methionine on Na+,K+-ATPase activity, indicating that Met inhibitory effect was probably mediated by free radical formation. Besides, we tested the in vitro effect of methionine on some parameters of oxidative stress, namely chemiluminescence, thiobarbituric acid reactive substances (TBARS), total radical-trapping antioxidant potential (TRAP), as well as on the antioxidant enzyme activities catalase, glutathione peroxidase and superoxide dismutase in rat hippocampus. We observed that methionine significantly increased chemiluminescence and TBARS, decreased TRAP, but did not change the activity of the antioxidant enzymes. These findings suggest that reduction of Na+,K+-ATPase activity and induction of oxidative stress may be involved in the brain damage observed in human hypermethioninemia.
在本研究中,我们调查了海马匀浆暴露于蛋氨酸对大鼠突触质膜上Na +,K + -ATP酶活性的影响。结果表明,蛋氨酸显著降低了该酶的活性。我们还评估了单独孵育谷胱甘肽(GSH)和生育三烯酚(α-生育酚)或与蛋氨酸联合孵育对Na +,K + -ATP酶活性的影响。所测试的抗氧化剂本身并未改变酶活性,但阻止了蛋氨酸对Na +,K + -ATP酶活性的抑制作用,表明蛋氨酸的抑制作用可能是由自由基形成介导的。此外,我们测试了蛋氨酸对氧化应激的一些参数的体外影响,即化学发光、硫代巴比妥酸反应性物质(TBARS)、总自由基捕获抗氧化能力(TRAP),以及对大鼠海马中抗氧化酶过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶活性的影响。我们观察到,蛋氨酸显著增加了化学发光和TBARS,降低了TRAP,但未改变抗氧化酶的活性。这些发现表明,Na +,K + -ATP酶活性的降低和氧化应激的诱导可能与人类高蛋氨酸血症中观察到的脑损伤有关。