Homocysteine induces oxidative cytotoxicity in Cu,Zn-superoxide dismutase mutant motor neuronal cell

Neuroreport
Jung-Joon SungKwang-Woo Lee

Abstract

Mutations in human Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis (FALS) cases. The mechanism of late-onset disease manifestation despite the innate mutation has no clear explanation. The relationship between homocysteine (HC) and amyotrophic lateral sclerosis (ALS) has not been investigated, in spite of the similarity in their pathogenesis. We investigated the effect of HC on the motor neuronal cell-line transfected with SOD1 of either wild-type or one of two mutant forms (G93A and A4V). In the MTT assay, HC induced significant cytotoxicity in A4V, but not in G93A, as compared with wild-type, even at the physiological concentration of 10 microM. This HC-induced cytotoxicity was inhibited by the antioxidant trolox and the Cu (I) chelator bathocuproinedisulfonate. Here we show that the vulnerability of the A4 V mutant involves the cytotoxic copper-mediated pathway, and that HC may be a lifelong precipitating factor in some forms of FALS, suggesting the possible treatment modality with vitamin supplements.

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Citations

Aug 8, 2009·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·F ValentinoV La Bella
Jan 18, 2011·Toxicology and Applied Pharmacology·Richelle A HemendingerBenjamin Rix Brooks
Dec 23, 2015·Journal of Cell Communication and Signaling·Ahmet MenteseSelim Demir
Jul 28, 2005·The European Journal of Neuroscience·Seong-Ho KohSeung Hyun Kim
Apr 13, 2005·Brain Research·Fernanda BonattoJosé Cláudio Fonseca Moreira
Mar 6, 2012·Genetic Testing and Molecular Biomarkers·Ali SazciHalil Atilla Idrisoglu
Jun 25, 2009·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Stefano ZoccolellaGiancarlo Logroscino
Oct 24, 2002·Current Opinion in Clinical Nutrition and Metabolic Care·Amy Cameron, Jeffrey Rosenfeld

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