Creatine affects in vitro electrophysiological maturation of neuroblasts and protects them from oxidative stress

Sartini, Stefania; Sestili, Piero; Colombo, Evelin; Martinelli, Chiara; Bartolini, Fanny; Ciuffoli, Stefano; Lattanzi, Davide; Sisti, Davide; Cuppini, Riccardo

doi:10.1002/jnr.22762

Cited by 17 publications

(10 citation statements)

References 53 publications

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“…Rises in creatine in the absence of phosphocreatine may be indicative of an impaired metabolism due to an energy-depleted system [23]. Creatine has also been found to have a neuro-protectant role as an anti-oxidant in hypoxic chick spinal cord neuron cultures [24]. Fumarate and 2-oxogluterate are components of the citric acid cycle important for energy metabolism [25].…”

Section: Discussionmentioning

confidence: 99%

Identifying Hypoxia in a Newborn Piglet Model Using Urinary NMR Metabolomic Profiling

et al. 2013

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Establishing the severity of hypoxic insult during the delivery of a neonate is key step in the determining the type of therapy administered. While successful therapy is present, current methods for assessing hypoxic injuries in the neonate are limited. Urine Nuclear Magnetic Resonance (NMR) metabolomics allows for the rapid non-invasive assessment of a multitude breakdown products of physiological processes. In a newborn piglet model of hypoxia, we used NMR spectroscopy to determine the levels of metabolites in urine samples, which were correlated with physiological measurements. Using PLS-DA analysis, we identified 13 urinary metabolites that differentiated hypoxic versus nonhypoxic animals (1-methylnicotinamide, 2-oxoglutarate, alanine, asparagine, betaine, citrate, creatine, fumarate, hippurate, lactate, N-acetylglycine, N-carbamoyl-β-alanine, and valine). Using this metabolomic profile, we then were able to blindly identify hypoxic animals correctly 84% of the time compared to nonhypoxic controls. This was better than using physiologic measures alone. Metabolomic profiling of urine has potential for identifying neonates that have undergone episodes of hypoxia.

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Section: Discussionmentioning

confidence: 99%

Identifying Hypoxia in a Newborn Piglet Model Using Urinary NMR Metabolomic Profiling

et al. 2013

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“…The potential for therapeutic creatine augmentation in the setting of cardiac myopathies was demonstrated in mouse model of myocardial infraction (Lygate et al 2012) and it has recently been reviewed elsewhere (Zervou et al 2015). Cr supplementation has been reported to have a protective effect in neurons, myoblasts, and cardiomyocytes in culture when the cells are subjected to hypoxic and increased oxidative stressors (Adcock et al 1999(Adcock et al , 2002Balestrino et al 2002;Caretti et al 2010;Santacruz et al 2015a;Sartini et al 2012). Similar positive results have been reported in studies of the effects of Cr supplementation in animal models of neonatal hypoxia (Allah Yar et al 2015;Ellery et al 2013), and in a study with human volunteers that evaluated the Fig.…”

Section: Introductionmentioning

confidence: 96%

Structural correlates of the creatine transporter function regulation: the undiscovered country

Santacruz

Jacobs²

2016

Amino Acids

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Creatine (Cr) and phosphocreatine constitute an energy shuttle that links ATP production in mitochondria to subcellular locations of ATP consumption. Cells in tissues that are reliant on this energy shuttle, such as myocytes and neurons, appear to have very limited ability to synthesize creatine. Therefore, these cells depend on Cr uptake across the cell membrane by a specialized creatine transporter (CrT solute carrier SLC6A8) in order to maintain intracellular creatine levels. Cr supplementation has been shown to have a beneficial effect in numerous in vitro and in vivo models, particularly in cases of oxidative stress, and is also widely used by athletes as a performance enhancement nutraceutical. Intracellular creatine content is maintained within narrow limits. However, the physiological and cellular mechanisms that mediate Cr transport during health and disease (such as cardiac failure) are not understood. In this narrative mini-review, we summarize the last three decades of research on CrT structure, function and regulation.

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“…2010; Sartini et al. 2012). Given the role of Cr/PCr in maintaining ATP levels in the cell, we sought to quantify the effects of Cr supplementation, as well as that of AMPK activation alone or in combination with Cr supplementation on ATP, PCr, and Cr content.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned previously, Cr supplementation has been reported to have a protective effect in both neurons, myoblasts, and cardiomyocytes in culture when subjected to hypoxic and increased oxidative stressors (Balestrino et al 1999(Balestrino et al , 2002Adcock et al 2002;Caretti et al 2010;Sartini et al 2012). Given the role of Cr/PCr in maintaining ATP levels in the cell, we sought to quantify the effects of Cr supplementation, as well as that of AMPK activation alone or in combination with Cr supplementation on ATP, PCr, and Cr content.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

et al. 2017

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Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m. Pharmacological activation of AMP‐activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF‐1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF‐1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia.

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Creatine affects in vitro electrophysiological maturation of neuroblasts and protects them from oxidative stress

Cited by 17 publications

References 53 publications

Identifying Hypoxia in a Newborn Piglet Model Using Urinary NMR Metabolomic Profiling

Identifying Hypoxia in a Newborn Piglet Model Using Urinary NMR Metabolomic Profiling

Structural correlates of the creatine transporter function regulation: the undiscovered country

Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation

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