Caspase-3 Activity and Autophagy Expression in the Development of Neuronal Resistance to Glutamate Toxicity

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Resumo

Two periods of autophagy activation, differently significant for the development of resistance, were demonstrated in the model of neuronal resistance to the toxic effect of glutamate (deprivation of trophic factors). The autophagy inhibitor 3-methyladenine (3-MA) at a concentration of 1.25 mM significantly suppresses resistance development, but only if applied immediately after deprivation of trophic factors. Inhibition of autophagy with 3-MA immediately during deprivation does not affect resistance production. In addition, activation of autophagy is responsible for the decrease in caspase-3 activity, although the mechanism of this process remains unclear. We hypothesize that resistance production in neurons is mediated by a decrease in caspase-3 activity as a result of autophagy activation.

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Sobre autores

O. Aleksandrova

Brain Research Center at Research Center of Neurology; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences

Email: al_yakovlev@rambler.ru
Rússia, Moscow; Moscow

D. Kuznetsova

First Moscow State Medical University named after I.M. Sechenov

Email: al_yakovlev@rambler.ru
Rússia, Moscow

A. Lyzhin

Brain Research Center at Research Center of Neurology

Email: al_yakovlev@rambler.ru
Rússia, Moscow

L. Khaspekov

Brain Research Center at Research Center of Neurology

Email: al_yakovlev@rambler.ru
Rússia, Moscow

N. Gulyaeva

Brain Research Center at Research Center of Neurology

Email: al_yakovlev@rambler.ru
Rússia, Moscow

A. Yakovlev

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences; Moscow Research & Clinical Center for Neuropsychiatry, Moscow Research & Clinical Center for Neuropsychiatry

Autor responsável pela correspondência
Email: al_yakovlev@rambler.ru
Rússia, Moscow; Moscow

Bibliografia

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2. Fig. 1. The number of propidium iodide-positive cells in the visual field (reflects the intensity of neuronal death) after exposure to glutamate and the expression of proteins mTOR, caspase-9 and caspase-3 in sister cultures without the addition of glutamate. For details of the experiment, see the methods section. a — the number of propidium iodide-positive cells; b — expression of the protein mTOR, IE; c — expression of caspase-9, IE; d — expression of caspase-3, IE. The group designations are shown in the legend below the drawing. The concentration of 3-MA is 1.25 mM. The reliability of the differences: *p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.0005.

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3. Fig. 2. Activity of caspase-3 and cathepsin B in neuron cultures before and after exposure to glutamate. For details of the experiment, see the methods section. a — activity of caspase-3, pmol/min/mg of protein in cells without the addition of glutamate; b — activity of cathepsin B, nmol/min/mg of protein in cells without the addition of glutamate; c — activity of caspase-3, pmol/min/mg of protein in cells after the addition of glutamate; d — activity of cathepsin In, nmol/min/mg of protein in cells after addition of glutamate. The group designations are shown in the legend below the drawing. The concentration of 3-MA is 1.25 mM. The reliability of the differences: *p < 0.05, **p < 0.01.

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