Effect of sydnone SYD-1, a mesoionic compound, on energy-linked functions of rat liver mitochondria
| Autor: | Aurea Echevarria, Gerusa Clazer Halila, Alice Carneiro Belém, Maria Eliane Merlin Rocha, Glaucia Regina Martinez, Maria Benigna M. Oliveira, Silvia Maria Suter Correia Cadena, Eva Gunilla Skare Carnieri, Guilhermina Rodrigues Noleto |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cell Respiration Respiratory chain Mitochondria Liver Oxidative phosphorylation Mitochondrion Toxicology Sodium Glutamate Sydnones Membrane Potentials chemistry.chemical_compound Valinomycin Animals Rats Wistar Inner mitochondrial membrane Adenosine Triphosphatases Ions Oxadiazoles Molecular Structure Glutamate dehydrogenase Cell Membrane General Medicine Rats chemistry Biochemistry Oligomycins Mitochondrial Swelling Sydnone |
| Zdroj: | Chemico-Biological Interactions. 169:160-170 |
| ISSN: | 0009-2797 |
| DOI: | 10.1016/j.cbi.2007.06.003 |
| Popis: | An important antitumour effect of SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) has been shown. We now report the effects of this mesoionic compound on mitochondrial metabolism. SYD-1 (1.5 micromol mg(-1) protein) dose-dependently inhibited the respiratory rate by 65% and 40% in state 3 using sodium glutamate and succinate, respectively, as substrates. Phosphorylation efficiency was depressed by SYD-1, as evidenced by stimulation of the state 4 respiratory rate, which was more accentuated with glutamate ( approximately 180%) than with succinate ( approximately 40%), with 1.5 micromol mg(-1) protein of SYD-1. As a consequence of the effects on states 3 and 4, the RCC and ADP/O ratios were lowered by SYD-1 using both substrates, although this effect was stronger with glutamate. The formation of membrane electrical potential was inhibited by approximately 50% (1.5 micromol SYD-1mg(-1) protein). SYD-1 interfered with the permeability of the inner mitochondrial membrane, as demonstrated by assays of mitochondrial swelling in the presence of sodium acetate and valinomycin +K(+). SYD-1 (1.5 micromol mg(-1) protein) inhibited glutamate completely and succinate energized-mitochondrial swelling by 80% in preparations containing sodium acetate. The swelling of de-energized mitochondria induced by K(+) and valinomycin was inhibited by 20% at all concentrations of SYD-1. An analysis of the segments of the respiratory chain suggested that the SYD-1 inhibition site goes beyond the complex I and includes complexes III and IV. Glutamate dehydrogenase was inhibited by 20% with SYD-1 (1.5 micromol mg(-1) protein). The hydrolytic activity of complex F(1)F(o) ATPase in intact mitochondria was greatly increased ( approximately 450%) in the presence of SYD-1. Our results show that SYD-1 depresses the efficiency of electron transport and oxidative phosphorylation, suggesting that these effects may be involved in its antitumoural effect. |
| Databáze: | OpenAIRE |
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