Reactive oxygen at the heart of metabolism

Murray, Thomas; Ahmad, Aminah N.; Brewer, Alison C.

doi:10.1016/j.tcm.2013.09.003

Cited by 24 publications

(10 citation statements)

References 71 publications

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“…Indeed, substrates play an essential role in metabolism since lactate hinders the oxidation of lipids while fatty acids are able to repress the processes involved in the use of carbohydrates ( Werner et al, 1989 ). As a result in the fetus, only 15% of total energy production derives from the use of fatty acids ( Lopaschuk and Jaswal, 2010 ), a substrate choice adapted to the low oxygen environment similar to the one encountered by the hypoxic adult hearts ( Patterson and Zhang, 2010 ; Murray et al, 2014 ). In addition to the impact of the substrate availability on fetal metabolism, the higher activity and specific regulations of glycolytic enzymes in this stage of development ( Jones and Rolph, 1985 ) favor the production of anaerobic ATP ( Bristow et al, 1987 ; Ascuitto and Ross-Ascuitto, 1996 ).…”

Section: How Different Is Energy Metabolism Between the Newborn And Tmentioning

confidence: 99%

“…Following the increase in mitochondrial mass, the postnatal heart also strengthens the mechanisms protecting the cells against possible oxidative damage ( Das et al, 1987 ; Bodi et al, 2017 ) since mitochondria are the main source of reactive oxygen species (ROS) ( Taverne et al, 2013 ). While the latter play an important role in maturation processes ( Murray et al, 2014 ), they can also cause intracellular damages affecting cardiomyocyte functions ( Tsutsui et al, 2011 ; Hafstad et al, 2013 ), thereby leading the cardiac muscle cell to develop defense mechanisms.…”

Section: The Postnatal Transition To a New Energy Statementioning

confidence: 99%

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Maturation of Cardiac Energy Metabolism During Perinatal Development

2018

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As one of the highest energy consumer organ in mammals, the heart has to be provided with a high amount of energy as soon as its first beats in utero. During the development of this organ, energy is produced within the cardiac muscle cell depending on substrate availability, oxygen pressure and cardiac workload that drastically change at birth. Thus, energy metabolism relying essentially on carbohydrates in fetal heart is very different from the adult one and birth is the trigger of a profound maturation which ensures the transition to a highly oxidative metabolism depending on lipid utilization. To face the substantial increase in cardiac workload resulting from the growth of the organism during the postnatal period, the heart not only develops its capacity for energy production but also undergoes a hypertrophic growth to adapt its contractile capacity to its new function. This leads to a profound cytoarchitectural remodeling of the cardiomyocyte which becomes a highly compartmentalized structure. As a consequence, within the mature cardiac muscle, energy transfer between energy producing and consuming compartments requires organized energy transfer systems that are established in the early postnatal life. This review aims at describing the major rearrangements of energy metabolism during the perinatal development.

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Section: How Different Is Energy Metabolism Between the Newborn And Tmentioning

confidence: 99%

Section: The Postnatal Transition To a New Energy Statementioning

confidence: 99%

Maturation of Cardiac Energy Metabolism During Perinatal Development

2018

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“…Oxidative stress has long been attributed to age related degenerative diseases [1] . Highly oxidized cellular milieu has been a common denominator for cardiovascular disorders like endothelial dysfunction, hypertrophy, myocyte loss, ischemia reperfusion injury and heart failure [2–4] . However, alleviating those conditions by antioxidants have largely been unsuccessful [5] .…”

Section: Introductionmentioning

confidence: 99%

Norepinephrine-induced apoptotic and hypertrophic responses in H9c2 cardiac myoblasts are characterized by different repertoire of reactive oxygen species generation

et al. 2015

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Despite recent advances, the role of ROS in mediating hypertrophic and apoptotic responses in cardiac myocytes elicited by norepinephrine (NE) is rather poorly understood. We demonstrate through our experiments that H9c2 cardiac myoblasts treated with 2 µM NE (hypertrophic dose) generate DCFH-DA positive ROS only for 2 h; while those treated with 100 µM NE (apoptotic dose) sustains generation for 48 h, followed by apoptosis. Though the levels of DCFH fluorescence were comparable at early time points in the two treatment sets, its quenching by DPI, catalase and MnTmPyP suggested the existence of a different repertoire of ROS. Both doses of NE also induced moderate levels of H2O2 but with different kinetics. Sustained but intermittent generation of highly reactive species detectable by HPF was seen in both treatment sets but no peroxynitrite was generated in either conditions. Sustained generation of hydroxyl radicals with no appreciable differences were noticed in both treatment sets. Nevertheless, despite similar profile of ROS generation between the two conditions, extensive DNA damage as evident from the increase in 8-OH-dG content, formation of γ-H2AX and PARP cleavage was seen only in cells treated with the higher dose of NE. We therefore conclude that hypertrophic and apoptotic doses of NE generate distinct but comparable repertoire of ROS/RNS leading to two very distinct downstream responses.

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“…Perhaps not coincidentally, it is also the time during which the mammalian heart begins to lose its ability to regenerate (19,20). Neonatal cardiomyocytes also undergo radical switches in metabolic pathways and contractile protein isoforms to fully commit to the mature differentiated phenotype (21,22). We understand surprisingly little about the mechanisms by which cell-cycle exit and terminal differentiation are coordinated, considering the importance of precisely executing these processes for adult cardiomyocyte homeostasis and function.…”

mentioning

confidence: 99%

Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors

Desjardins

Naya

2017

Journal of Biological Chemistry

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Cardiomyocytes acquire their primary specialized function (contraction) before exiting the cell cycle. In this regard, proliferation and differentiation must be precisely coordinated for proper cardiac morphogenesis. Here, we have investigated the complex transcriptional mechanisms employed by cardiomyocytes to coordinate antagonistic cell-cycle and differentiation gene programs through the molecular dissection of the core cardiac transcription factor, MEF2. Knockdown of individual MEF2 proteins, MEF2A, -C, and -D, in primary neonatal cardiomyocytes resulted in radically distinct and opposite effects on cellular homeostasis and gene regulation. MEF2A and MEF2D were absolutely required for cardiomyocyte survival, whereas MEF2C, despite its major role in cardiac morphogenesis and direct reprogramming, was dispensable for this process. Inhibition of MEF2A or -D also resulted in the activation of cell-cycle genes and down-regulation of markers of terminal differentiation. In striking contrast, the regulation of cell-cycle and differentiation gene programs by MEF2C was antagonistic to that of MEF2A and -D. Computational analysis of regulatory regions from MEF2 isoform-dependent gene sets identified the Notch and Hedgehog signaling pathways as key determinants in coordinating MEF2 isoform-specific control of antagonistic gene programs. These results reveal that mammalian MEF2 family members have distinct transcriptional functions in cardiomyocytes and suggest that these differences are critical for proper development and maturation of the heart. Analysis of MEF2 isoform-specific function in neonatal cardiomyocytes has yielded insight into an unexpected transcriptional regulatory mechanism by which these specialized cells utilize homologous members of a core cardiac transcription factor to coordinate cell-cycle and differentiation gene programs.

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Reactive oxygen at the heart of metabolism

Cited by 24 publications

References 71 publications

Maturation of Cardiac Energy Metabolism During Perinatal Development

Maturation of Cardiac Energy Metabolism During Perinatal Development

Norepinephrine-induced apoptotic and hypertrophic responses in H9c2 cardiac myoblasts are characterized by different repertoire of reactive oxygen species generation

Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors

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