Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans

Tarnopolsky, Mark A.; Parise, Gianni; Fu, Min-Hua; Brose, Andrea; Parshad, A.; Speer, Oliver; Wallimann, Theo

doi:10.1007/978-1-4615-0247-0_24

Cited by 23 publications

(23 citation statements)

References 30 publications

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“…Notably, Cr-supplemented, oxidatively-injured C2C12 had Cr and CrP levels even higher than those of either Cr-free, H 2 O 2 -treated cells or of controls at both DifD1 and 3. Finally, the 24 h Cr supplementation regimen did not affect the mRNA expression of the CRT (not shown), as compared to Cr-free cultures, a finding similar to that reported in vivo by Tarnopolsky et al [65].…”

Section: Intracellular Levels Of Cr/crp and Atpsupporting

confidence: 84%

Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts

Sestili¹,

Barbieri

Martinelli

et al. 2009

Molecular Nutrition Food Res

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Creatine (Cr), one of the most popular nutritional supplements among athletes, has been recently shown to prevent the cytotoxicity caused by different oxidative stressors in various mammalian cell lines, including C2C12 myoblasts, via a direct antioxidant activity. Here, the effect of Cr on the differentiating capacity of C2C12 cells exposed to H(2)O(2) has been investigated. Differentiation into myotubes was monitored using morphological, ultrastructural, and molecular techniques. Treatment with H(2)O(2) (1 h) not only caused a significant (30%) loss of cell viability, but also abrogated the myogenic ability of surviving C2C12. Cr-supplementation (24 h prior to H(2)O(2) treatment) was found to prevent these effects. Interestingly, H(2)O(2)-challenged cells preconditioned with the established antioxidants trolox or N-acetyl-cysteine, although cytoprotected, did not display the same differentiating ability characterizing oxidatively-injured, Cr-supplemented cells. Besides acting as an antioxidant, Cr increased the level of muscle regulatory factors and IGF1 (an effect partly refractory to oxidative stress), the cellular availability of phosphocreatine and seemed to exert some mitochondrially-targeted protective activity. It is concluded that Cr preserves the myogenic ability of oxidatively injured C2C12 via a pleiotropic mechanism involving not only its antioxidant capacity, but also the contribution to cell energy charge and effects at the transcriptional level which common bona fide antioxidants lack.

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Section: Intracellular Levels Of Cr/crp and Atpsupporting

confidence: 84%

Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts

Sestili¹,

Barbieri

Martinelli

et al. 2009

Molecular Nutrition Food Res

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“…Muscle also possesses a creatine transporter, but training does not appear to affect the amount of transporter proteins (Tarnopolski et al 2003), although this is not known with certainty because specific antibodies are lacking (Snow and Murphy 2003;Walzer et al 2002).…”

Section: Creatine Transportmentioning

confidence: 98%

Training-induced changes in membrane transport proteins of human skeletal muscle

Juel

2006

Eur J Appl Physiol

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Training improves human physical performance by inducing structural and cardiovascular changes, metabolic changes, and changes in the density of membrane transport proteins. This review focuses on the training-induced changes in proteins involved in sarcolemmal membrane transport. It is concluded that the same type of training affects many transport proteins, suggesting that all transport proteins increase with training, and that both sprint and endurance training in humans increase the density of most membrane transport proteins. There seems to be an upper limit for these changes: intense training for 6-8 weeks substantially increases the density of membrane proteins, whereas years of training (as performed by athletes) have no further effect. Studies suggest that training-induced changes at the protein level are important functionally. The underlying factors responsible for these changes in transport proteins might include changes in substrate concentration, but the existence of "exercise factors" mediating these responses is more likely. Exercise factors might include Ca(2+), mitogen-activated protein kinases, adenosine monophosphate kinases, other kinases, or interleukin-6. Although the magnitudes of training-induced changes have been investigated at the protein level, the underlying signal mechanisms have not been fully described.

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“…However, the combined Cr co-treatment during NH 4 + exposure resulted in the repression of AGAT expression, both at the mRNA and at the protein levels, but only in the NH 4 + -induced swollen astrocytes. Data are more controversial for SLC6A8, which is down-regulated at the protein level in skeletal muscles of rats fed with high dosages of Cr (Guerrero-Ontiveros & Wallimann, 1998), while this does not occur in humans, either at the mRNA or at the protein level (Tarnopolsky et al, 2003). For SLC6A8 protein, however, these studies have to be considered with caution as they used an anti-SLC6A8 antibody showing non-specific cross-reactivities (Speer et al, 2004).…”

Section: Regulation Of Agat and Slc6a8 Genes By Extracellular Cr Levelsmentioning

confidence: 99%

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency

Braissant

Cagnon

Monnet‐Tschudi

et al. 2008

Eur J of Neuroscience

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Hyperammonemic disorders in pediatric patients lead to poorly understood irreversible effects on the developing brain that may be life-threatening. We showed previously that some of these NH4+-induced irreversible effects might be due to impairment of axonal growth that can be protected under ammonium exposure by creatine co-treatment. The aim of the present work was thus to analyse how the genes of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), allowing creatine synthesis, as well as of the creatine transporter SLC6A8, allowing creatine uptake into cells, are regulated in rat brain cells under NH4+ exposure. Reaggregated brain cell three-dimensional cultures exposed to NH4Cl were used as an experimental model of hyperammonemia in the developing central nervous system (CNS). We show here that NH4+ exposure differentially alters AGAT, GAMT and SLC6A8 regulation, in terms of both gene expression and protein activity, in a cell type-specific manner. In particular, we demonstrate that NH4+ exposure decreases both creatine and its synthesis intermediate, guanidinoacetate, in brain cells, probably through the inhibition of AGAT enzymatic activity. Our work also suggests that oligodendrocytes are major actors in the brain in terms of creatine synthesis, trafficking and uptake, which might be affected by hyperammonemia. Finally, we show that NH4+ exposure induces SLC6A8 in astrocytes. This suggests that hyperammonemia increases blood-brain barrier permeability for creatine. This is normally limited due to the absence of SLC6A8 from the astrocyte feet lining microcapillary endothelial cells, and thus creatine supplementation may protect the developing CNS of hyperammonemic patients.

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Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans

Cited by 23 publications

References 30 publications

Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts

Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts

Training-induced changes in membrane transport proteins of human skeletal muscle

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency

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