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Lancel 2012 PLoS One

From Bioblast
Publications in the MiPMap
Lancel S, Montaigne D, Marechal X, Marciniak C, Hassoun SM, Decoster B, Ballot C, Blazejewski C, Corseaux D, Lescure B, Motterlini R, Neviere R (2012) Carbon monoxide improves cardiac function and mitochondrial population quality in a mouse model of metabolic syndrome. PLoS One 7:e41836.

Β» PMID: 22870253 Open Access

Lancel S, Montaigne D, Marechal X, Marciniak C, Hassoun SM, Decoster B, Ballot C, Blazejewski C, Corseaux D, Lescure B, Motterlini R, Neviere R (2012) PLoS One

Abstract: AIMS: Metabolic syndrome induces cardiac dysfunction associated with mitochondria abnormalities. As low levels of carbon monoxide (CO) may improve myocardial and mitochondrial activities, we tested whether a CO-releasing molecule (CORM-3) reverses metabolic syndrome-induced cardiac alteration through changes in mitochondrial biogenesis, dynamics and autophagy.

METHODS AND RESULTS: Mice were fed with normal diet (ND) or high-fat diet (HFD) for twelve weeks. Then, mice received two intraperitoneal injections of CORM-3 (10 mg x kg(-1)), with the second one given 16 hours after the first. Contractile function in isolated hearts and mitochondrial parameters were evaluated 24 hours after the last injection. Mitochondrial population was explored by electron microscopy. Changes in mitochondrial dynamics, biogenesis and autophagy were assessed by western-blot and RT-qPCR. Left ventricular developed pressure was reduced in HFD hearts. Mitochondria from HFD hearts presented reduced membrane potential and diminished ADP-coupled respiration. CORM-3 restored both cardiac and mitochondrial functions. Size and number of mitochondria increased in the HFD hearts but not in the CORM-3-treated HFD group. CORM-3 modulated HFD-activated mitochondrial fusion and biogenesis signalling. While autophagy was not activated in the HFD group, CORM-3 increased the autophagy marker LC3-II. Finally, ex vivo experiments demonstrated that autophagy inhibition by 3-methyladenine abolished the cardioprotective effects of CORM-3.

CONCLUSION: CORM-3 may modulate pathways controlling mitochondrial quality, thus leading to improvements of mitochondrial efficiency and HFD-induced cardiac dysfunction. β€’ Keywords: Metabolic syndrome, Normal diet, High-fat diet, Carbon Monoxide, CO-releasing molecule (CORM-3)

β€’ O2k-Network Lab: FR Lille Neviere R, FR Lille Lancel Steve


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression  Pathology: Other 

Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue, Isolated mitochondria 

Regulation: ADP  Coupling state: OXPHOS  Pathway:HRR: Oxygraph-2k