TY - JOUR
T1 - Acute lysine overload provokes protein oxidative damage and reduction of antioxidant defenses in the brain of infant glutaryl-CoA dehydrogenase deficient mice
T2 - A role for oxidative stress in GA i neuropathology
AU - Seminotti, Bianca
AU - Ribeiro, Rafael Teixeira
AU - Amaral, Alexandre Umpierrez
AU - Da Rosa, Mateus Struecker
AU - Pereira, Carolina Coffi
AU - Leipnitz, Guilhian
AU - Koeller, David M.
AU - Goodman, Stephen
AU - Woontner, Michael
AU - Wajner, Moacir
N1 - Funding Information:
This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - 470236/2012-4 , Programa de Apoio a Núcleos de Excelência (PRONEX) , Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) - 10/0031-1 , Pró-Reitoria de Pesquisa/Universidade Federal do Rio Grande do Sul (PROPESQ/UFRGS) - PIBIT 18489 , Financiadora de estudos e projetos (FINEP) , Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00 and Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCT-EN) - 573677/2008-5 .
PY - 2014/9/15
Y1 - 2014/9/15
N2 - 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.
AB - 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.
KW - 3-Hydroxyglutaric acid
KW - Antioxidant defenses
KW - Brain damage
KW - Glutaric acid
KW - Glutaric acidemia type I
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U2 - 10.1016/j.jns.2014.06.034
DO - 10.1016/j.jns.2014.06.034
M3 - Article
C2 - 24996493
AN - SCOPUS:84906793854
SN - 0022-510X
VL - 344
SP - 105
EP - 113
JO - Journal of the neurological sciences
JF - Journal of the neurological sciences
IS - 1-2
ER -