Homocysteinic acid causes oxidative stress in lymphocytes by potentiating toxic effect of NMDA.
Short-term incubation of lymphocytes with homocysteine or its oxidation product homocysteinic acid increased the formation of reactive oxygen species and cell necrosis (in case of homocysteinic acid). Effective concentration of homocysteine and homocysteinic acid (500 microM) significantly surpassed the level observed during hyperhomocysteinemia. The addition of homocysteinic acid in a nontoxic concentration of 100 microM potentiated the toxic effect of NMDA and led to massive cell death. During hyperhomocysteinemia the amount of these metabolites in the blood was much higher than in the brain. Oxidative stress produced by these substances can result from activation of NMDA glutamate receptors that were recently detected on lymphocytes.
Boldyrev
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Laboratory of Clinical Neurochemistry, Institute of Neurology, Russian Academy of Medical Sciences, Moscow. aaboldyrev@yahoo.com
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005434:Flow Cytometry; D005452:Fluoresceins; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006711:Homocystine / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D016202:N-Methylaspartate / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism
D005452:Fluoresceins; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D006710:Homocysteine; C007956:homocysteic acid; C053897:5(6)-carboxy-2',7'-dichlorofluorescein; D006711:Homocystine; D016202:N-Methylaspartate