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Gangliosides GM1 and GD1a normalize respiratory rates of rat brain mitochondria reduced by tert-butyl hydroperoxide

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Abstract

The rate of oxygen consumption by glutamate- and malate-energized rat brain mitochondria, which was stimulated by an uncoupler 2,4-dinitrophenol (DNP), declined in the presence of a prooxidant tert-butyl hydroperoxide. Preincubation with gangliosides GM1 or GD1a at micromolar (but not nanomolar) concentrations significantly slowed down this decline in the mitochondrial respiration, as shown by measuring absolute respiratory rates and ratios of the mitochondrial respiratory rate in the presence of DNP to the basal respiratory rate (V DNP/V 0). Gangliosides GM1 and GD1a also slowed down a decline in the DNP-stimulated mitochondrial respiration induced by long-term incubation (“aging”) of mitochondria on ice. The data obtained are likely to reflect a prooxidant-induced reduction in the activity of enzymes of the mitochondrial respiratory chain as well as a GM1- and GD1a-induced decrease in the degree of their inactivation. Interestingly, in the presence of the Trk receptor tyrosine kinase inhibitor (K252a) this effect of gangliosides was not manifested in any way. Our data suggest that the direct impact of gangliosides on mitochondrial signaling pathways, specifically on the Trk receptor tyrosine kinase, plays a certain role in the mechanism of their protective effect on cerebral neurons and, probably, neuroglia.

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Correspondence to N. F. Avrova.

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Original Russian Text © S.M. Korotkov, T.V. Sokolova, N.F. Avrova, 2017, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2017, Vol. 53, No. 3, pp. 178—184.

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Korotkov, S.M., Sokolova, T.V. & Avrova, N.F. Gangliosides GM1 and GD1a normalize respiratory rates of rat brain mitochondria reduced by tert-butyl hydroperoxide. J Evol Biochem Phys 53, 200–207 (2017). https://doi.org/10.1134/S0022093017030048

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  • DOI: https://doi.org/10.1134/S0022093017030048

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