The Experts below are selected from a list of 222807 Experts worldwide ranked by ideXlab platform

Xavier Leverve - One of the best experts on this subject based on the ideXlab platform.

  • the ros production induced by a reverse electron flux at respiratory Chain Complex 1 is hampered by metformin
    Journal of Bioenergetics and Biomembranes, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, Myehia Elmir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Δ m), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate–malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate–malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate–malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • The ROS production induced by a reverse-electron flux at respiratory-Chain Complex 1 is hampered by metformin.
    Journal of Bioenergetics, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, M-yehia El-mir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Delta Phi(m)), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate-malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate-malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate-malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells.
    Journal of Biological Chemistry, 2001
    Co-Authors: Christiane Chauvin, Xavier Leverve, Frédéric De Oliveira, Xavier Ronot, Mireille Mousseau, Eric Fontaine
    Abstract:

    The permeability transition pore (PTP) is a mitochondrial inner membrane Ca(2+)-sensitive channel that plays a key role in different models of cell death. Because functional links between the PTP and the respiratory Chain Complex I have been reported, we have investigated the effects of rotenone on PTP regulation in U937 and KB cells. We show that rotenone was more potent than cyclosporin A at inhibiting Ca(2+)-induced PTP opening in digitonin-permeabilized cells energized with succinate. Consistent with PTP regulation by electron flux through Complex I, the effect of rotenone persisted after oxidation of pyridine nucleotides by duroquinone. tert-butyl hydroperoxide induced PTP opening in intact cells (as shown by mitochondrial permeabilization to calcein and cobalt), as well as cytochrome c release and cell death. All these events were prevented by rotenone or cyclosporin A. These data demonstrate that respiratory Chain Complex I plays a key role in PTP regulation in vivo and confirm the importance of PTP opening in the commitment to cell death.

  • Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory Chain Complex I.
    Journal of Biological Chemistry, 2000
    Co-Authors: Mohamad Yehia El-mir, Véronique Nogueira, Eric Fontaine, Nicole Avéret, Michel Rigoulet, Xavier Leverve
    Abstract:

    We report here a new mitochondrial regulation occurring only in intact cells. We have investigated the effects of dimethylbiguanide on isolated rat hepatocytes, permeabilized hepatocytes, and isolated liver mitochondria. Addition of dimethylbiguanide decreased oxygen consumption and mitochondrial membrane potential only in intact cells but not in permeabilized hepatocytes or isolated mitochondria. Permeabilized hepatocytes after dimethylbiguanide exposure and mitochondria isolated from dimethylbiguanide pretreated livers or animals were characterized by a significant inhibition of oxygen consumption with Complex I substrates (glutamate and malate) but not with Complex II (succinate) or Complex IV (N,N,N',N'-tetramethyl-1, 4-phenylenediamine dihydrochloride (TMPD)/ascorbate) substrates. Studies using functionally isolated Complex I obtained from mitochondria isolated from dimethylbiguanide-pretreated livers or rats further confirmed that dimethylbiguanide action was located on the respiratory Chain Complex I. The dimethylbiguanide effect was temperature-dependent, oxygen consumption decreasing by 50, 20, and 0% at 37, 25, and 15 degrees C, respectively. This effect was not affected by insulin-signaling pathway inhibitors, nitric oxide precursor or inhibitors, oxygen radical scavengers, ceramide synthesis inhibitors, or chelation of intra- or extracellular Ca(2+). Because it is established that dimethylbiguanide is not metabolized, these results suggest the existence of a new cell-signaling pathway targeted to the respiratory Chain Complex I with a persistent effect after cessation of the signaling process.

Eric Fontaine - One of the best experts on this subject based on the ideXlab platform.

  • the ros production induced by a reverse electron flux at respiratory Chain Complex 1 is hampered by metformin
    Journal of Bioenergetics and Biomembranes, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, Myehia Elmir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Δ m), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate–malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate–malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate–malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • The ROS production induced by a reverse-electron flux at respiratory-Chain Complex 1 is hampered by metformin.
    Journal of Bioenergetics, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, M-yehia El-mir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Delta Phi(m)), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate-malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate-malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate-malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells.
    Journal of Biological Chemistry, 2001
    Co-Authors: Christiane Chauvin, Xavier Leverve, Frédéric De Oliveira, Xavier Ronot, Mireille Mousseau, Eric Fontaine
    Abstract:

    The permeability transition pore (PTP) is a mitochondrial inner membrane Ca(2+)-sensitive channel that plays a key role in different models of cell death. Because functional links between the PTP and the respiratory Chain Complex I have been reported, we have investigated the effects of rotenone on PTP regulation in U937 and KB cells. We show that rotenone was more potent than cyclosporin A at inhibiting Ca(2+)-induced PTP opening in digitonin-permeabilized cells energized with succinate. Consistent with PTP regulation by electron flux through Complex I, the effect of rotenone persisted after oxidation of pyridine nucleotides by duroquinone. tert-butyl hydroperoxide induced PTP opening in intact cells (as shown by mitochondrial permeabilization to calcein and cobalt), as well as cytochrome c release and cell death. All these events were prevented by rotenone or cyclosporin A. These data demonstrate that respiratory Chain Complex I plays a key role in PTP regulation in vivo and confirm the importance of PTP opening in the commitment to cell death.

  • Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory Chain Complex I.
    Journal of Biological Chemistry, 2000
    Co-Authors: Mohamad Yehia El-mir, Véronique Nogueira, Eric Fontaine, Nicole Avéret, Michel Rigoulet, Xavier Leverve
    Abstract:

    We report here a new mitochondrial regulation occurring only in intact cells. We have investigated the effects of dimethylbiguanide on isolated rat hepatocytes, permeabilized hepatocytes, and isolated liver mitochondria. Addition of dimethylbiguanide decreased oxygen consumption and mitochondrial membrane potential only in intact cells but not in permeabilized hepatocytes or isolated mitochondria. Permeabilized hepatocytes after dimethylbiguanide exposure and mitochondria isolated from dimethylbiguanide pretreated livers or animals were characterized by a significant inhibition of oxygen consumption with Complex I substrates (glutamate and malate) but not with Complex II (succinate) or Complex IV (N,N,N',N'-tetramethyl-1, 4-phenylenediamine dihydrochloride (TMPD)/ascorbate) substrates. Studies using functionally isolated Complex I obtained from mitochondria isolated from dimethylbiguanide-pretreated livers or rats further confirmed that dimethylbiguanide action was located on the respiratory Chain Complex I. The dimethylbiguanide effect was temperature-dependent, oxygen consumption decreasing by 50, 20, and 0% at 37, 25, and 15 degrees C, respectively. This effect was not affected by insulin-signaling pathway inhibitors, nitric oxide precursor or inhibitors, oxygen radical scavengers, ceramide synthesis inhibitors, or chelation of intra- or extracellular Ca(2+). Because it is established that dimethylbiguanide is not metabolized, these results suggest the existence of a new cell-signaling pathway targeted to the respiratory Chain Complex I with a persistent effect after cessation of the signaling process.

Michel Rigoulet - One of the best experts on this subject based on the ideXlab platform.

  • the ros production induced by a reverse electron flux at respiratory Chain Complex 1 is hampered by metformin
    Journal of Bioenergetics and Biomembranes, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, Myehia Elmir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Δ m), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate–malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate–malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate–malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • The ROS production induced by a reverse-electron flux at respiratory-Chain Complex 1 is hampered by metformin.
    Journal of Bioenergetics, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, M-yehia El-mir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Delta Phi(m)), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate-malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate-malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate-malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory Chain Complex I.
    Journal of Biological Chemistry, 2000
    Co-Authors: Mohamad Yehia El-mir, Véronique Nogueira, Eric Fontaine, Nicole Avéret, Michel Rigoulet, Xavier Leverve
    Abstract:

    We report here a new mitochondrial regulation occurring only in intact cells. We have investigated the effects of dimethylbiguanide on isolated rat hepatocytes, permeabilized hepatocytes, and isolated liver mitochondria. Addition of dimethylbiguanide decreased oxygen consumption and mitochondrial membrane potential only in intact cells but not in permeabilized hepatocytes or isolated mitochondria. Permeabilized hepatocytes after dimethylbiguanide exposure and mitochondria isolated from dimethylbiguanide pretreated livers or animals were characterized by a significant inhibition of oxygen consumption with Complex I substrates (glutamate and malate) but not with Complex II (succinate) or Complex IV (N,N,N',N'-tetramethyl-1, 4-phenylenediamine dihydrochloride (TMPD)/ascorbate) substrates. Studies using functionally isolated Complex I obtained from mitochondria isolated from dimethylbiguanide-pretreated livers or rats further confirmed that dimethylbiguanide action was located on the respiratory Chain Complex I. The dimethylbiguanide effect was temperature-dependent, oxygen consumption decreasing by 50, 20, and 0% at 37, 25, and 15 degrees C, respectively. This effect was not affected by insulin-signaling pathway inhibitors, nitric oxide precursor or inhibitors, oxygen radical scavengers, ceramide synthesis inhibitors, or chelation of intra- or extracellular Ca(2+). Because it is established that dimethylbiguanide is not metabolized, these results suggest the existence of a new cell-signaling pathway targeted to the respiratory Chain Complex I with a persistent effect after cessation of the signaling process.

Cécile Batandier - One of the best experts on this subject based on the ideXlab platform.

  • the ros production induced by a reverse electron flux at respiratory Chain Complex 1 is hampered by metformin
    Journal of Bioenergetics and Biomembranes, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, Myehia Elmir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Δ m), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate–malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate–malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate–malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

  • The ROS production induced by a reverse-electron flux at respiratory-Chain Complex 1 is hampered by metformin.
    Journal of Bioenergetics, 2006
    Co-Authors: Cécile Batandier, Eric Fontaine, Michel Rigoulet, Bruno Guigas, Dominique Detaille, M-yehia El-mir, Xavier Leverve
    Abstract:

    Mitochondrial reactive oxygen species (ROS) production was investigated in mitochondria extracted from liver of rats treated with or without metformin, a mild inhibitor of respiratory Chain Complex 1 used in type 2 diabetes. A high rate of ROS production, fully suppressed by rotenone, was evidenced in non-phosphorylating mitochondria in the presence of succinate as a single Complex 2 substrate. This ROS production was substantially lowered by metformin pretreatment and by any decrease in membrane potential (Delta Phi(m)), redox potential (NADH/NAD), or phosphate potential, as induced by malonate, 2,4-dinitrophenol, or ATP synthesis, respectively. ROS production in the presence of glutamate-malate plus succinate was lower than in the presence of succinate alone, but higher than in the presence of glutamate-malate. Moreover, while rotenone both increased and decreased ROS production at Complex 1 depending on forward (glutamate-malate) or reverse (succinate) electron flux, no ROS overproduction was evidenced in the forward direction with metformin. Therefore, we propose that reverse electron flux through Complex 1 is an alternative pathway, which leads to a specific metformin-sensitive ROS production.

G Dos A S Santos - One of the best experts on this subject based on the ideXlab platform.

  • α tocopheryl succinate inhibits the mitochondrial respiratory Chain Complex i and is as effective as arsenic trioxide or atra against acute promyelocytic leukemia in vivo
    Leukemia, 2012
    Co-Authors: G Dos A S Santos, R Abreu S E Lima, Cezar R Pestana, Anderson Lima, P S Scheucher, Carolina Hassibe Thome, H L Gimenesteixeira, Barbara A Santanalemos, Antonio R Lucenaaraujo
    Abstract:

    The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory Chain Complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory Complex I was highlighted as potential target for anticancer therapy.