Difference between revisions of "Marechal 2011 Clin Sci (Lond)"

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{{Publication
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|title=Marechal X, Montaigne D, Marciniak C, Marchetti P, Hassoun SM, Beauvillain JC, Lancel S, Neviere R (2011) Doxorubicin-induced cardiac dysfunction is attenuated by ciclosporin treatment in mice through improvements in mitochondrial bioenergetics. Clin Sci (Lond)121:405-413.
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|info=http://www.ncbi.nlm.nih.gov/pubmed/21605084
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|authors=Marechal X, Montaigne D, Marciniak C, Marchetti P, Hassoun SM, Beauvillain JC, Lancel S, Neviere R
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|year=2011
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|journal=Clin Sci (Lond)
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|abstract=We tested whether inhibition of mitochondrial membrane potential dissipation by CsA (ciclosporin A) would prevent doxorubicin-induced myocardial and mitochondrial dysfunction. Acute and subchronic models of doxorubicin exposition were performed in mice with either a single intraperitoneal bolus (10 mg/kg of body weight, intraperitoneal) or one injection of 4 mg·kg(-1) of body weight·week(-1) during 5 weeks. Follow-up was at 1.5 weeks and 16 weeks in acute and subchronic models respectively. Mice received either CsA (1 mg/kg of body weight, intraperitoneal on alternate days) or saline until follow-up. Heart function was evaluated by echocardiography. Mitochondrial measurements included oxygen consumption, membrane potential and externally added calcium-induced mitochondrial permeability transition. Mitochondrial mass was evaluated by transmission electronic microscopy and mtDNA (mitochondrial DNA) content. Mitochondrial dynamics were detected as the expression of GTPases involved in mitochondrial fusion and fission. In both the acute and chronic models, doxorubicin decreased left ventricular fractional shortening and survival. Heart function and survival were improved by CsA, but not by tacrolimus (FK506), a ciclosporin derivative with no inhibitory effect on the mitochondrial transition pore. In the acute model, doxorubicin exposure was associated with increased mtDNA content, mitochondrial fragmentation and changes in mitochondrial fusion- and fission-related transcripts [increases in Mfn2 (mitofusin 2), Opa1 (optic atrophy 1 homologue) and Fis1 (fission 1 homologue), and no changes in Drp1 (dynamin 1-like)]. CsA did not alter mitochondrial biogenesis, but prevented mitochondrial fragmentation and partially restored the mitochondrial energy-producing capacity. These findings suggest that in vivo CsA treatment may limit MPTP (mitochondrial permeability transition pore) opening, mitochondrial potential loss and contractile depression in acute and chronic models of cardiac toxicity induced by doxorubicin.
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|keywords=biogenesis, ciclosporin, doxorubicin, energetics, heart, mitochondrial transition permeability
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|mipnetlab=FR Lille Neviere R
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}}
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{{Labeling
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|instruments=Oxygraph-2k
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|injuries=RONS; Oxidative Stress, Mitochondrial Disease; Degenerative Disease and Defect
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|organism=Mouse
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|tissues=Cardiac Muscle
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|preparations=Permeabilized Cell or Tissue; Homogenate
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|topics=Respiration; OXPHOS; ETS Capacity, Coupling; Membrane Potential
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}}

Revision as of 15:21, 30 November 2011

Publications in the MiPMap
Marechal X, Montaigne D, Marciniak C, Marchetti P, Hassoun SM, Beauvillain JC, Lancel S, Neviere R (2011) Doxorubicin-induced cardiac dysfunction is attenuated by ciclosporin treatment in mice through improvements in mitochondrial bioenergetics. Clin Sci (Lond)121:405-413.

» http://www.ncbi.nlm.nih.gov/pubmed/21605084

Marechal X, Montaigne D, Marciniak C, Marchetti P, Hassoun SM, Beauvillain JC, Lancel S, Neviere R (2011) Clin Sci (Lond)

Abstract: We tested whether inhibition of mitochondrial membrane potential dissipation by CsA (ciclosporin A) would prevent doxorubicin-induced myocardial and mitochondrial dysfunction. Acute and subchronic models of doxorubicin exposition were performed in mice with either a single intraperitoneal bolus (10 mg/kg of body weight, intraperitoneal) or one injection of 4 mg·kg(-1) of body weight·week(-1) during 5 weeks. Follow-up was at 1.5 weeks and 16 weeks in acute and subchronic models respectively. Mice received either CsA (1 mg/kg of body weight, intraperitoneal on alternate days) or saline until follow-up. Heart function was evaluated by echocardiography. Mitochondrial measurements included oxygen consumption, membrane potential and externally added calcium-induced mitochondrial permeability transition. Mitochondrial mass was evaluated by transmission electronic microscopy and mtDNA (mitochondrial DNA) content. Mitochondrial dynamics were detected as the expression of GTPases involved in mitochondrial fusion and fission. In both the acute and chronic models, doxorubicin decreased left ventricular fractional shortening and survival. Heart function and survival were improved by CsA, but not by tacrolimus (FK506), a ciclosporin derivative with no inhibitory effect on the mitochondrial transition pore. In the acute model, doxorubicin exposure was associated with increased mtDNA content, mitochondrial fragmentation and changes in mitochondrial fusion- and fission-related transcripts [increases in Mfn2 (mitofusin 2), Opa1 (optic atrophy 1 homologue) and Fis1 (fission 1 homologue), and no changes in Drp1 (dynamin 1-like)]. CsA did not alter mitochondrial biogenesis, but prevented mitochondrial fragmentation and partially restored the mitochondrial energy-producing capacity. These findings suggest that in vivo CsA treatment may limit MPTP (mitochondrial permeability transition pore) opening, mitochondrial potential loss and contractile depression in acute and chronic models of cardiac toxicity induced by doxorubicin.

Keywords: biogenesis, ciclosporin, doxorubicin, energetics, heart, mitochondrial transition permeability

O2k-Network Lab: FR Lille Neviere R


Labels:

Stress:
"RONS; Oxidative Stress" is not in the list of possible values (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) for this property.
,
"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list of possible values (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) for this property.
 

Organism: Mouse 

Tissue;cell:
"Cardiac Muscle" is not in the list of possible values (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, Genital, Other cell lines, CHO, HEK, HeLa, Neuroblastoma, Fibroblast, HUVEC, Macrophage-derived, Lymphocyte, Platelet, Stem cells) for this property.
  Preparation:
"Permeabilized Cell or Tissue; Homogenate" is not in the list of possible values (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, Intact cells) for this property.
  Regulation:
"Respiration; OXPHOS; ETS Capacity" is not in the list of possible values (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, Ion;substrate transport, mt-Membrane potential, Oxygen kinetics, PCr;Cr, pH, Phosphate, Redox state, Substrate, Temperature, Threshold;excess capacity, Uncoupler, Fatty acid, Amino acid, Q-junction effect) for this property.
,
"Coupling; Membrane Potential" is not in the list of possible values (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, Ion;substrate transport, mt-Membrane potential, Oxygen kinetics, PCr;Cr, pH, Phosphate, Redox state, Substrate, Temperature, Threshold;excess capacity, Uncoupler, Fatty acid, Amino acid, Q-junction effect) for this property.
 


HRR: Oxygraph-2k