Seminotti Bianca, Ribeiro Rafael Teixeira, Amaral Alexandre Umpierrez, da Rosa Mateus Struecker, Pereira Carolina Coffi, Leipnitz Guilhian, Koeller David M, Goodman Stephen, Woontner Michael, Wajner Moacir
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Department of Pediatrics, Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
J Neurol Sci. 2014 Sep 15;344(1-2):105-13. doi: 10.1016/j.jns.2014.06.034. Epub 2014 Jun 22.
We evaluated the antioxidant defense system and protein oxidative damage in the brain and liver of 15-day-old GCDH deficient knockout (Gcdh(-/-)) mice following an acute intraperitoneal administration of Lys (8 μmol/g). We determined reduced glutathione (GSH) concentrations, sulfhydryl content, carbonyl formation and the activities of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in the brain and liver of these animals. 2',7'-dihydrodichlorofluorescein (DCFH) oxidation was also measured as an index of free radical formation. The only parameters altered in Gcdh(-/-) compared to wild type (Gcdh(+/+)) mice were a reduction of liver GSH concentrations and of brain sulfhydryl content. Acute Lys injection provoked a decrease of GSH concentration in the brain and sulfhydryl content in the liver, and an increase in carbonyl formation in the brain and liver of Gcdh(-/-) mice. Lys administration also induced a decrease of all antioxidant enzyme activities in the brain, as well as an increase of the activities of SOD and CAT in the liver of Gcdh(-/-) mice. Finally, Lys elicited a marked increase of DCFH oxidation in the brain and liver. It is concluded that Lys overload compromises the brain antioxidant defenses and induces protein oxidation probably secondary to reactive species generation in infant Gcdh(+/+) mice.
我们评估了15日龄的GCDH缺陷敲除（Gcdh(-/-)）小鼠在腹腔注射Lys（8 μmol/g）后，其大脑和肝脏中的抗氧化防御系统以及蛋白质氧化损伤情况。我们测定了这些动物大脑和肝脏中还原型谷胱甘肽（GSH）浓度、巯基含量、羰基形成以及抗氧化酶谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽还原酶（GR）的活性。还测定了2',7'-二氢二氯荧光素（DCFH）氧化情况作为自由基形成的指标。与野生型（Gcdh(+/+)）小鼠相比，Gcdh(-/-)小鼠中唯一改变的参数是肝脏GSH浓度降低和大脑巯基含量降低。急性注射Lys导致Gcdh(-/-)小鼠大脑中GSH浓度降低、肝脏中巯基含量降低，以及大脑和肝脏中羰基形成增加。给予Lys还导致Gcdh(-/-)小鼠大脑中所有抗氧化酶活性降低，以及肝脏中SOD和CAT活性增加。最后，Lys引起大脑和肝脏中DCFH氧化显著增加。结论是，Lys过载损害了幼龄Gcdh(+/+)小鼠的大脑抗氧化防御，并可能继发于活性物质生成而诱导蛋白质氧化。
