Sgaravatti Angela M, Vargas Bethânia A, Zandoná Bernardo R, Deckmann Kátia B, Rockenbach Francieli J, Moraes Tarsila B, Monserrat José M, Sgarbi Mirian B, Pederzolli Carolina D, Wyse Angela T S, Wannmacher Clóvis M D, Wajner Moacir, Dutra-Filho Carlos Severo
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Int J Dev Neurosci. 2008 Oct;26(6):551-9. doi: 10.1016/j.ijdevneu.2008.05.007. Epub 2008 May 28.
Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. In tyrosinemia type II, high levels of tyrosine are correlated with eyes, skin and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study, we investigated whether oxidative stress is elicited by l-tyrosine in cerebral cortex homogenates of 14-day-old Wistar rats. The in vitro effect of 0.1-4.0mM l-tyrosine was studied on the following oxidative stress parameters: total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), ascorbic acid content, reduced glutathione (GSH) content, spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), thiol-disulfide redox state (SH/SS ratio), protein carbonyl content, formation of DNA-protein cross-links, and the activities of the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glucose-6-phosphate dehydrogenase (G6PDH). TRAP, TAR, ascorbic acid content, SH/SS ratio and CAT activity were significantly diminished, while formation of DNA-protein cross-link was significantly enhanced by l-tyrosine in vitro. In contrast, l-tyrosine did not affect the other parameters of oxidative stress evaluated. These results indicate that l-tyrosine decreases enzymatic and non-enzymatic antioxidant defenses, changes the redox state and stimulates DNA damage in cerebral cortex of young rats in vitro. This suggests that oxidative stress may represent a pathophysiological mechanism in tyrosinemic patients, in which this amino acid accumulates.
酪氨酸在酪氨酸分解代谢的先天性缺陷中会蓄积，尤其是在II型酪氨酸血症中，患病患者的组织和生理体液中的酪氨酸水平会大幅升高。在II型酪氨酸血症中，高水平的酪氨酸与眼睛、皮肤和中枢神经系统紊乱有关。鉴于这些疾病中脑损伤的机制尚不清楚，在本研究中，我们调查了14日龄Wistar大鼠大脑皮层匀浆中的L-酪氨酸是否会引发氧化应激。研究了0.1-4.0mM L-酪氨酸对以下氧化应激参数的体外影响：总自由基捕获抗氧化能力（TRAP）、总抗氧化反应性（TAR）、抗坏血酸含量、还原型谷胱甘肽（GSH）含量、自发化学发光、硫代巴比妥酸反应性物质（TBA-RS）、硫醇-二硫键氧化还原状态（SH/SS比值）、蛋白质羰基含量、DNA-蛋白质交联的形成，以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和葡萄糖-6-磷酸脱氢酶（G6PDH）的活性。体外实验中，L-酪氨酸使TRAP、TAR、抗坏血酸含量、SH/SS比值和CAT活性显著降低，而DNA-蛋白质交联的形成则显著增强。相比之下，L-酪氨酸对所评估的其他氧化应激参数没有影响。这些结果表明，L-酪氨酸在体外会降低幼鼠大脑皮层中的酶促和非酶促抗氧化防御能力，改变氧化还原状态并刺激DNA损伤。这表明氧化应激可能是酪氨酸血症患者的一种病理生理机制，在这类患者中这种氨基酸会蓄积。
