Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: Down-regulation of the expression of creatine transporter isoforms in skeletal muscle

Guerrero-Ontiveros, Maria Lourdes; Wallimann, Theo

doi:10.1007/978-1-4615-5653-4_30

Cited by 95 publications

(118 citation statements)

References 82 publications

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“…The reasons for the lack of response are unclear but may be related to the extremely high doses (up to 5% in the diet) used previously. Thus we are not able to evaluate whether the decrease in CrT protein content observed by Guerrero-Ontiveros and Wallimann (18), who fed rats 4% Cr for 3 mo from a young age, results in the predictable decrease in Cr uptake. On the other hand, there was a response during prolonged Cr feeding that warrants consideration.…”

Section: Discussionmentioning

confidence: 90%

“…Despite a sustained elevated plasma Cr concentration of many times normal during prolonged Cr supplementation (19,35), muscle Cr content remains relatively constant thereafter. Accelerated uptake of Cr appears to occur initially, followed by a decline, possibly related to a de-cline in CrT number (18,45) and the modulation of CrT activity associated with an increased [Cr] i , if the relationship illustrated in Fig. 9 (soleus and red gastrocnemius) can be extended to above-normal [Cr] i .…”

Section: Discussionmentioning

confidence: 98%

“…CrT protein expression has been shown to be downregulated in skeletal muscle of some myopathies (37) and in cardiac muscle during heart failure (29). Similarly, CrT protein expression is lower in skeletal muscle of rats when dietary Cr supplementation was begun at 3 wk of age (18). Furthermore, cultured L6 myoblasts incubated with 5 mM Cr for 24 h decrease the maximal velocity but not the Michaelis-Menton constant of Cr uptake suggesting that the number of available transporters decreases but the affinity of the transporter for Cr does not change (24).…”

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confidence: 99%

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Muscle creatine uptake and creatine transporter expression in response to creatine supplementation and depletion

Brault

Abraham

Terjung

2003

Journal of Applied Physiology

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The total creatine pool size [Crtotal; creatine (Cr) + phosphocreatine (PCr)] is crucial for optimal energy utilization in skeletal muscle, especially at the onset of exercise and during intense contractions. The Crtotal likely is controlled by long-term modulation of Cr uptake via the sodium-dependent Cr transporter (CrT). To test this hypothesis, adult male Sprague-Dawley rats were fed 1% Cr, their muscle Crtotal was reduced by ∼85% [1% β-guanidinoproprionic acid (β-GPA)], or their muscle Crtotal was repleted (1% Cr after β-GPA depletion). Cr uptake was assessed by skeletal muscle 14C-Cr accumulation to Cr and PCr by using hindlimb perfusion, and CrT protein content was assessed by Western blot. Cr uptake rate decreased with dietary Cr supplementation in the white gastrocnemius (WG; 45%) only. Depletion of muscle Crtotal to ∼15% of normal increased Cr uptake in the soleus (21%) and red gastrocnemius (22%), corresponding to 70–150% increases in muscle CrT content. In contrast, the inherently lower Cr uptake rate in the WG was unchanged with depletion of muscle Crtotal even though CrT band density was increased by 230%. Thus there was no direct relationship between apparent muscle CrT abundance and Cr uptake rates. However, Cr uptake rates scaled inversely with decreases in muscle Crtotal in the high-oxidative muscle types but not in the WG. This implies that factors controlling Cr uptake are different among fiber types. These observations may help explain the influence of initial muscle Crtotal, time dependency, and variations in muscle Crtotal accumulation during Cr supplementation.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Muscle creatine uptake and creatine transporter expression in response to creatine supplementation and depletion

Brault

Abraham

Terjung

2003

Journal of Applied Physiology

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“…18 ± 21 In animal models of several neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) 22 and Huntington's disease, 23 creatine has proven to be a remarkably potent neuroprotective agent. Orally supplemented creatine is transported by a speci®c creatine transporter into muscle and neural tissues 24 as measured non-invasively by 31 P-NMP spectroscopy, giving rise to a signi®cantly increased PCr/ATP ratio in the rat brain 25 or by 1H-NMR spectroscopy in either creatine-de®cient patients 26 or healthy subjects, 27 showing that total creatine concentration is elevated in the brain after creatine supplementation. In a recent study with several animal species the elevation by creatine supplementation of total creatine into various organs including the brain has been con®rmed by chemical analysis.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of oral creatine supplementation on spinal cord injury in rats

et al. 2002

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Study design: To evaluate a potential protective e ect of increased creatine levels in spinal cord injury (SCI) in an animal model. Objectives: Acute SCI initiates a series of cellular and molecular events in the injured tissue leading to further damage in the surrounding area. This secondary damage is partly due to ischemia and a fatal intracellular loss of energy. Phospho-creatine in conjunction with the creatine kinase isoenzyme system acts as a potent intracellular energy bu er. Oral creatine supplementation has been shown to elevate the phospho-creatine content in brain and muscle tissue, leading to neuroprotective e ects and increased muscle performance. Setting: Zurich, Switzerland. Methods: Twenty adult rats were fed for 4 weeks with or without creatine supplemented nutrition before undergoing a moderate spinal cord contusion. Results: Following an initial complete hindlimb paralysis, rats of both groups substantially recovered within 1 week. However, creatine fed animals scored 2.8 points better than the controls in the BBB open ®eld locomotor score (11.9 and 9.1 points respectively after 1 week; P=0.035, and 13 points compared to 11.4 after 2 weeks). The histological examination 2 weeks after SCI revealed that in all rats a cavity had developed which was comparable in size between the groups. In creatine fed rats, however, a signi®cantly smaller amount of scar tissue surrounding the cavity was found. Conclusions: Thus creatine treatment seems to reduce the spread of secondary injury. Our results favour a pretreatment of patients with creatine for neuroprotection in cases of elective intramedullary spinal surgery. Further studies are needed to evaluate the bene®t of immediate creatine administration in case of acute spinal cord or brain injury.

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“…This is achieved, in large part, through uptake by the high-affinity creatine transporter (CrT) driven by the cotransport of sodium and chloride ions (12,20,30). Both CrT mRNA (20,31,38,40) and protein (19,31,47) are found in most mammalian tissues, with relatively high amounts in skeletal muscle, heart, and brain.…”

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confidence: 99%

Creatine uptake and creatine transporter expression among rat skeletal muscle fiber types

Brault

Terjung

2003

American Journal of Physiology-Cell Physiology

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Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: Down-regulation of the expression of creatine transporter isoforms in skeletal muscle

Cited by 95 publications

References 82 publications

Muscle creatine uptake and creatine transporter expression in response to creatine supplementation and depletion

Muscle creatine uptake and creatine transporter expression in response to creatine supplementation and depletion

Protective effects of oral creatine supplementation on spinal cord injury in rats

Creatine uptake and creatine transporter expression among rat skeletal muscle fiber types

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