Muller 2013 Exp Neurol: Difference between revisions
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{{Publication | {{Publication | ||
|title=Muller AP, Haas CB, Camacho-Pereira J, Brochier AW, Gnoatto J, Zimmer ER, de Souza DO, Galina A, Portela LV (2013) Insulin prevents mitochondrial generation of | |title=Muller AP, Haas CB, Camacho-Pereira J, Brochier AW, Gnoatto J, Zimmer ER, de Souza DO, Galina A, Portela LV (2013) Insulin prevents mitochondrial generation of H<sub>2</sub>O<sub>2</sub> in rat brain. Exp Neurol 247:66-72. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23499835 PMID: 23499835] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23499835 PMID: 23499835 Open Access] | ||
|authors=Muller AP, Haas CB, Camacho-Pereira J, Brochier AW, Gnoatto J, Zimmer ER, de Souza DO, Galina A, Portela LV | |authors=Muller AP, Haas CB, Camacho-Pereira J, Brochier AW, Gnoatto J, Zimmer ER, de Souza DO, Galina A, Portela LV | ||
|year=2013 | |year=2013 | ||
|journal=Exp Neurol | |journal=Exp Neurol | ||
|abstract=The mitochondrial electron transport system ( | |abstract=The mitochondrial electron transport system (ET-pathway) is a main source of cellular ROS, including hydrogen peroxide (HβOβ). The production of HβOβ also involves the mitochondrial membrane potential (ΞΞ¨m) and oxygen consumption. Impaired insulin signaling causes oxidative neuronal damage and places the brain at risk of neurodegeneration. We evaluated whether insulin signaling cross-talks with ET-pathway components (complexes I and FβFβATP synthase) and ΞΞ¨m to regulate mitochondrial HβOβ production, in tissue preparations from rat brain. Insulin (50 to 100 ng/mL) decreased HβOβ production in synaptosomal preparations in high Na(+) buffer (polarized state), stimulated by glucose and pyruvate, without affecting the oxygen consumption. In addition, insulin (10 to 100 ng/mL) decreased HβOβ production induced by succinate in synaptosomes in high K(+) (depolarized state), whereas wortmannin and LY290042, inhibitors of the PI3K pathway, reversed this effect; heated insulin had no effect. Insulin decreased HβOβ production when complexes I and FβFβATP synthase were inhibited by rotenone and oligomycin respectively suggesting a target effect on complex III. Also, insulin prevented the generation of maximum level of βΞ¨m induced by succinate. The PI3K inhibitors and heated insulin maintained the maximum level of βΞ¨m induced by succinate in synaptosomes in a depolarized state. Similarly, insulin decreased ROS production in neuronal cultures. In mitochondrial preparations, insulin neither modulated H<sub>2</sub>O<sub>2</sub> production or oxygen consumption. In conclusion, the normal downstream insulin receptor signaling is necessary to regulate complex III of ET-pathway avoiding the generation of maximal βΞ¨m and increased mitochondrial H<sub>2</sub>O<sub>2</sub> production. | ||
|keywords=Brain metabolism, H | |keywords=Brain metabolism, H<sub>2</sub>O<sub>2</sub> production, Insulin signaling, Mitochondria | ||
|mipnetlab=BR Rio de Janeiro Galina A, BR | |mipnetlab=BR Rio de Janeiro Galina A, BR Criciuma Muller AP | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, mt-Medicine | |||
|organism=Rat | |||
|tissues=Nervous system | |||
|couplingstates=LEAK, OXPHOS, ET | |||
|pathways=N, S | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 17:05, 27 March 2018
Muller AP, Haas CB, Camacho-Pereira J, Brochier AW, Gnoatto J, Zimmer ER, de Souza DO, Galina A, Portela LV (2013) Insulin prevents mitochondrial generation of H2O2 in rat brain. Exp Neurol 247:66-72. |
Muller AP, Haas CB, Camacho-Pereira J, Brochier AW, Gnoatto J, Zimmer ER, de Souza DO, Galina A, Portela LV (2013) Exp Neurol
Abstract: The mitochondrial electron transport system (ET-pathway) is a main source of cellular ROS, including hydrogen peroxide (HβOβ). The production of HβOβ also involves the mitochondrial membrane potential (ΞΞ¨m) and oxygen consumption. Impaired insulin signaling causes oxidative neuronal damage and places the brain at risk of neurodegeneration. We evaluated whether insulin signaling cross-talks with ET-pathway components (complexes I and FβFβATP synthase) and ΞΞ¨m to regulate mitochondrial HβOβ production, in tissue preparations from rat brain. Insulin (50 to 100 ng/mL) decreased HβOβ production in synaptosomal preparations in high Na(+) buffer (polarized state), stimulated by glucose and pyruvate, without affecting the oxygen consumption. In addition, insulin (10 to 100 ng/mL) decreased HβOβ production induced by succinate in synaptosomes in high K(+) (depolarized state), whereas wortmannin and LY290042, inhibitors of the PI3K pathway, reversed this effect; heated insulin had no effect. Insulin decreased HβOβ production when complexes I and FβFβATP synthase were inhibited by rotenone and oligomycin respectively suggesting a target effect on complex III. Also, insulin prevented the generation of maximum level of βΞ¨m induced by succinate. The PI3K inhibitors and heated insulin maintained the maximum level of βΞ¨m induced by succinate in synaptosomes in a depolarized state. Similarly, insulin decreased ROS production in neuronal cultures. In mitochondrial preparations, insulin neither modulated H2O2 production or oxygen consumption. In conclusion, the normal downstream insulin receptor signaling is necessary to regulate complex III of ET-pathway avoiding the generation of maximal βΞ¨m and increased mitochondrial H2O2 production. β’ Keywords: Brain metabolism, H2O2 production, Insulin signaling, Mitochondria
β’ O2k-Network Lab: BR Rio de Janeiro Galina A, BR Criciuma Muller AP
Labels: MiParea: Respiration, mt-Medicine
Organism: Rat
Tissue;cell: Nervous system
Coupling state: LEAK, OXPHOS, ET Pathway: N, S HRR: Oxygraph-2k