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Neurochemical Evidence that Lysine Inhibits Synaptic Na+,K+-ATPase Activity and Provokes Oxidative Damage in Striatum of Young Rats In vivo

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Abstract

Lysine (Lys) accumulation in tissues and biological fluids is the biochemical hallmark of patients affected by familial hyperlysinemia (FH) and other inherited metabolic disorders. In the present study we investigated the effects of acute administration of Lys on relevant parameters of energy metabolism and oxidative stress in striatum of young rats. We verified that Lys in vivo intrastriatal injection did not change the citric acid cycle function and creatine kinase activity, but, in contrast, significantly inhibited synaptic Na+,K+-ATPase activity in striatum prepared 2 and 12 h after injection. Moreover, Lys induced lipid peroxidation and diminished the concentrations of glutathione 2 h after injection. These effects were prevented by the antioxidant scavengers melatonin and the combination of α-tocopherol and ascorbic acid. Lys also inhibited glutathione peroxidase activity 12 h after injection. Therefore it is assumed that inhibition of synaptic Na+,K+-ATPase and oxidative damage caused by brain Lys accumulation may possibly contribute to the neurological manifestations of FH and other neurometabolic conditions with high concentrations of this amino acid.

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Acknowledgments

This work was supported by grants from CNPq, PRONEX II, FAPERGS, PROPESQ/UFRGS, FINEP research grant Rede Instituto Brasileiro de Neurociência (IBN-Net) # 01.06.0842-00 and INCT-EN.

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  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Rio Grande do Sul, Rua Ramiro Barcelos N° 2600—Anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Bianca Seminotti, Carolina Gonçalves Fernandes, Guilhian Leipnitz, Alexandre Umpierrez Amaral, Ângela Zanatta & Moacir Wajner

  2. Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Moacir Wajner

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  1. Bianca Seminotti
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  2. Carolina Gonçalves Fernandes
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Correspondence to Moacir Wajner.

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Seminotti, B., Fernandes, C.G., Leipnitz, G. et al. Neurochemical Evidence that Lysine Inhibits Synaptic Na+,K+-ATPase Activity and Provokes Oxidative Damage in Striatum of Young Rats In vivo. Neurochem Res 36, 205–214 (2011). https://doi.org/10.1007/s11064-010-0302-4

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