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Difference between revisions of "Nunez-Figueredo 2014 Brain Res Bull"

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peak at βˆ’0.71 V, which is close to that of oxygen (βˆ’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
peak at βˆ’0.71 V, which is close to that of oxygen (βˆ’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.
|keywords=JM-20, Antioxidan,t Mitochondria, Synaptosome,s Neuroprotector, Brain ischemia
|keywords=JM-20, Antioxidan,t Mitochondria, Synaptosomes, Neuroprotector, Brain ischemia, Amplex red
|mipnetlab=BR Criciuma Muller AP
}}
}}
{{Labeling
{{Labeling
|area=Respiration
|area=Respiration
|injuries=Ischemia-reperfusion
|organism=Rat
|organism=Rat
|tissues=Nervous system
|tissues=Nervous system
|preparations=Isolated mitochondria
|preparations=Isolated mitochondria
|injuries=Ischemia-reperfusion
|topics=Calcium
|topics=Calcium
|couplingstates=ETS
|couplingstates=ET
|substratestates=CI, CII, ROX
|pathways=N, S
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=Labels
}}
}}

Latest revision as of 16:05, 27 March 2018

Publications in the MiPMap
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.

Β» PMID: 25305343

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 ΞΌM. 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 ΞΌM and 2.452 ΞΌM, respectively. JM-20 was unable to react directly with H2O2 or with superoxide anion radicals but displayed a cathodic reduction peak at βˆ’0.71 V, which is close to that of oxygen (βˆ’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. β€’ Keywords: JM-20, Antioxidan, t Mitochondria, Synaptosomes, Neuroprotector, Brain ischemia, Amplex red

β€’ O2k-Network Lab: BR Criciuma Muller AP


Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Regulation: Calcium  Coupling state: ET  Pathway: N, S  HRR: Oxygraph-2k