Difference between revisions of "Nunez-Figueredo 2014 Brain Res Bull"
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and synaptosomes isolated from rat brains. JM-20 inhibited succinate-mediated H<sub>2</sub>O<sub>2</sub> generation in both mitochondria and synaptosomes incubated in depolarized (high K<sub>+</sub>) medium at extremely low micromolar concentration and with identical IC<sub>50</sub> values of 0.91 μM. JM-20 also repressed glucoseinduced | and synaptosomes isolated from rat brains. JM-20 inhibited succinate-mediated H<sub>2</sub>O<sub>2</sub> generation in both mitochondria and synaptosomes incubated in depolarized (high K<sub>+</sub>) medium at extremely low micromolar concentration and with identical IC<sub>50</sub> values of 0.91 μM. JM-20 also repressed glucoseinduced | ||
H<sub>2</sub>O<sub>2</sub> generation stimulated by rotenone or by antimycin A in synaptosomes incubated in high sodium-polarized medium at extremely low IC<sub>50</sub> values of 0.395 μM and 2.452 μM, respectively. JM-20 was unable to react directly with H<sub>2</sub>O<sub>2</sub> or with superoxide anion radicals but displayed a cathodic reduction | H<sub>2</sub>O<sub>2</sub> generation stimulated by rotenone or by antimycin A in synaptosomes incubated in high sodium-polarized medium at extremely low IC<sub>50</sub> values of 0.395 μM and 2.452 μM, respectively. JM-20 was unable to react directly with H<sub>2</sub>O<sub>2</sub> or with superoxide anion radicals but displayed a cathodic reduction | ||
peak at −0.71 V, which is close to that of oxygen (−0.8 V), indicating high electron affinity. JM-20 also inhibited uncoupled respiration in mitochondria or synaptosomes and was a more effective inhibitor in the presence of the respiratory substrates glutamate/malate than in the presence of succinate. JM-20 also prevented Ca<sup>2+</ | peak at −0.71 V, which is close to that of oxygen (−0.8 V), indicating high electron affinity. JM-20 also inhibited uncoupled respiration in mitochondria or synaptosomes and was a more effective inhibitor in the presence of the respiratory substrates glutamate/malate than in the presence of succinate. JM-20 also prevented Ca<sup>2+</sup> -induced mitochondrial permeability transition pore opening, membrane potential dissipation and cytochrome ''c'' release, which are key pathogenic events during stroke. This molecule also prevented Ca<sup>2+</sup> influx into synaptosomes and mitochondria; the former effect was a consequence of the latter because JM-20 inhibition followed the patterns of carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP), which is a classic mitochondrial uncoupler. Because the mitochondrion is considered an important source and target of neuronal cell death signaling after an ischemic insult, the antioxidant and protective effects of JM-20 against the deleterious effects of Ca<sup>2+</sup> observed at the mitochondrial level in this study may endow this molecule with the ability to succeed in mitochondrion-targeted strategies | ||
to combat ischemic brain damage. | to combat ischemic brain damage. | ||
}} | }} | ||
Revision as of 17:52, 9 December 2014
| Nunez-Figueredo Y, Pardo-Andreu GL, Ramirez-Sanchez J, Delgado-Hernandez R, Ochoa-Rodriguez E, Verdecia-Reyes Y, Naal Z, Muller AP, Portela LV, Souza DO (2014) Antioxidant effects of JM-20 on rat brain mitochondria and synaptosomes: Mitoprotection against Ca2+-induced mitochondrial impairment. Brain Res Bull 109: 68-76. |
Nunez-Figueredo Y, Pardo-Andreu GL, Ramirez-Sanchez J, Delgado-Hernandez R, Ochoa-Rodriguez E, Verdecia-Reyes Y, Naal Z, Muller AP, Portela LV, Souza DO (2014) Brain Res Bull
Abstract: Because mitochondrial oxidative stress and impairment are important mediators of neuronal damage in neurodegenerative diseases and in brain ischemia/reperfusion, in the present study, we evaluated the antioxidant and mitoprotective effect of a new promising neuroprotective molecule, JM-20, in mitochondria and synaptosomes isolated from rat brains. JM-20 inhibited succinate-mediated H2O2 generation in both mitochondria and synaptosomes incubated in depolarized (high K+) medium at extremely low micromolar concentration and with identical IC50 values of 0.91 μM. JM-20 also repressed glucoseinduced H2O2 generation stimulated by rotenone or by antimycin A in synaptosomes incubated in high sodium-polarized medium at extremely low IC50 values of 0.395 μM and 2.452 μM, respectively. JM-20 was unable to react directly with H2O2 or with superoxide anion radicals but displayed a cathodic reduction peak at −0.71 V, which is close to that of oxygen (−0.8 V), indicating high electron affinity. JM-20 also inhibited uncoupled respiration in mitochondria or synaptosomes and was a more effective inhibitor in the presence of the respiratory substrates glutamate/malate than in the presence of succinate. JM-20 also prevented Ca2+ -induced mitochondrial permeability transition pore opening, membrane potential dissipation and cytochrome c release, which are key pathogenic events during stroke. This molecule also prevented Ca2+ influx into synaptosomes and mitochondria; the former effect was a consequence of the latter because JM-20 inhibition followed the patterns of carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP), which is a classic mitochondrial uncoupler. Because the mitochondrion is considered an important source and target of neuronal cell death signaling after an ischemic insult, the antioxidant and protective effects of JM-20 against the deleterious effects of Ca2+ observed at the mitochondrial level in this study may endow this molecule with the ability to succeed in mitochondrion-targeted strategies to combat ischemic brain damage.
Labels: MiParea: Respiration
HRR: Oxygraph-2k
