Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration

Bianca Seminotti, Mateus Struecker da Rosa, Carolina Gonçalves Fernandes, Alexandre Umpierrez Amaral, Luisa Macedo Braga, Guilhian Leipnitz, Diogo Onofre Gomes de Souza, Michael Woontner, David Koeller, Stephen Goodman, Moacir Wajner

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In the present work we evaluated a variety of indicators of oxidative stress in distinct brain regions (striatum, cerebral cortex and hippocampus), the liver, and heart of 30-day-old glutaryl-CoA dehydrogenase deficient (Gcdh-/-) mice. The parameters evaluated included thiobarbituric acid-reactive substances (TBA-RS), 2-7-dihydrodichlorofluorescein (DCFH) oxidation, sulfhydryl content, and reduced glutathione (GSH) concentrations. We also measured the activities of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G6PD). Under basal conditions glutaric (GA) and 3-OH-glutaric (3OHGA) acids were elevated in all tissues of the Gcdh-/- mice, but were essentially absent in WT animals. In contrast there were no differences between WT and Gcdh-/- mice in any of the indicators or oxidative stress under basal conditions. Following a single intra-peritoneal (IP) injection of lysine (Lys) there was a moderate increase of brain GA concentration in Gcdh-/- mice, but no change in WT. Lys injection had no effect on brain 3OHGA in either WT or Gcdh-/- mice. The levels of GA and 3OHGA were approximately 40% higher in striatum compared to cerebral cortex in Lys-treated mice. In the striatum, Lys administration provoked a marked increase of lipid peroxidation, DCFH oxidation, SOD and GR activities, as well as significant reductions of GSH levels and GPx activity, with no alteration of sulfhydryl content, CAT and G6PD activities. There was also evidence of increased lipid peroxidation and SOD activity in the cerebral cortex, along with a decrease of GSH levels, but to a lesser extent than in the striatum. In the hippocampus only mild increases of SOD activity and DCFH oxidation were observed. In contrast, Lys injection had no effect on any of the parameters of oxidative stress in the liver or heart of Gcdh-/- or WT animals. These results indicate that in Gcdh-/- mice cerebral tissue, particularly the striatum, is at greater risk for oxidative stress than peripheral tissues following Lys administration.

Original languageEnglish (US)
Pages (from-to)31-38
Number of pages8
JournalMolecular Genetics and Metabolism
Volume106
Issue number1
DOIs
StatePublished - May 2012

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Glutaryl-CoA Dehydrogenase
Oxidative stress
Lysine
Brain
Oxidative Stress
Superoxide Dismutase
Cerebral Cortex
Glutathione Reductase
Glucosephosphate Dehydrogenase
Tissue
Glutathione Peroxidase
Liver
Oxidation
Catalase
Animals
Lipid Peroxidation
Injections
Hippocampus
Lipids
Thiobarbituric Acid Reactive Substances

Keywords

  • 3-Hydroxyglutaric acid
  • Gcdh mice
  • Glutaric acid
  • Glutaric acidemia type I
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Seminotti, B., da Rosa, M. S., Fernandes, C. G., Amaral, A. U., Braga, L. M., Leipnitz, G., ... Wajner, M. (2012). Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration. Molecular Genetics and Metabolism, 106(1), 31-38. https://doi.org/10.1016/j.ymgme.2012.03.002

Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration. / Seminotti, Bianca; da Rosa, Mateus Struecker; Fernandes, Carolina Gonçalves; Amaral, Alexandre Umpierrez; Braga, Luisa Macedo; Leipnitz, Guilhian; de Souza, Diogo Onofre Gomes; Woontner, Michael; Koeller, David; Goodman, Stephen; Wajner, Moacir.

In: Molecular Genetics and Metabolism, Vol. 106, No. 1, 05.2012, p. 31-38.

Research output: Contribution to journalArticle

Seminotti, B, da Rosa, MS, Fernandes, CG, Amaral, AU, Braga, LM, Leipnitz, G, de Souza, DOG, Woontner, M, Koeller, D, Goodman, S & Wajner, M 2012, 'Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration', Molecular Genetics and Metabolism, vol. 106, no. 1, pp. 31-38. https://doi.org/10.1016/j.ymgme.2012.03.002
Seminotti, Bianca ; da Rosa, Mateus Struecker ; Fernandes, Carolina Gonçalves ; Amaral, Alexandre Umpierrez ; Braga, Luisa Macedo ; Leipnitz, Guilhian ; de Souza, Diogo Onofre Gomes ; Woontner, Michael ; Koeller, David ; Goodman, Stephen ; Wajner, Moacir. / Induction of oxidative stress in brain of glutaryl-CoA dehydrogenase deficient mice by acute lysine administration. In: Molecular Genetics and Metabolism. 2012 ; Vol. 106, No. 1. pp. 31-38.
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