Uptake of creatine by cultured cells

Daly, Marie M.; Seifter, Sam

doi:10.1016/0003-9861(80)90182-4

Cited by 66 publications

(48 citation statements)

References 16 publications

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“…Even though the skeletal muscle phenotypes of all mammals are not identical, we suspect that these rates of creatine uptake are characteristic for mammalian muscle, including humans. As in previous work (13,27,33,51), most of the creatine uptake was Na dependent and therefore assignable to the actions of the Na-dependent CrT. Similar to the observations of some (32,47,51), but in contrast to others (22,33,41), there was no influence of insulin on creatine uptake rate, implying that insulin has little if any direct membrane effect on creatine transport.…”

Section: Discussionsupporting

confidence: 85%

“…The large differences in fiber Cr total concentration and the measured CrT content among these phenotypes permit an assessment of factors important to cellular creatine metabolism. Creatine uptakes measured previously in cultured myoblasts (13,27,33), cultured myotubes (13,27), incubated whole muscle (17,51), and giant sarcolemmal vesicles (47) have indicated that the apparent K m of the CrT for creatine is fairly low, on the order of 50-120 mol/l. Our results are consistent, with near maximal rates of creatine uptake observed in the physiological range of 100-300 mol/l creatine (75-140 nmol ⅐ h Ϫ1 ⅐ g Ϫ1 ).…”

Section: Discussionmentioning

confidence: 88%

“…Creatine uptake rates measured in cell lines overexpressing the cloned CrT (14,20,32,37), cultured myoblasts (13,27,33), giant sarcolemmal vesicles (47), and incubated muscle (51) reveal an apparent MichaelisMenten constant (K m) for transport of 30-188 M. Because this is near or below the typical plasma creatine concentration for mammals, it is probable that the transporter may be nearly saturated in vivo. This implies that creatine uptake would be proportional to the CrT content of the myocyte.…”

mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

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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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“…Interestingly, tissues that contain high levels of creatine/phosphocreatine do not appear to synthesize their own creatine (1). A specific uptake system for creatine was first identified in skeletal muscle (2) and later shown to be present in various cultured cell preparations (3,4) as well as human monocytes and macrophages (5).…”

Section: Transportersmentioning

confidence: 99%

Substituted Cysteine Accessibility of the Third Transmembrane Domain of the Creatine Transporter

Dodd

Christie

2005

Journal of Biological Chemistry

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Twenty-two amino acid residues from transmembrane domain 3 of the creatine transporter were replaced, one at a time, with cysteine. The background for mutagenesis was a C144S mutant retaining ϳ75% of wild-type transport activity but resistant to methanethiosulfonate (MTS) reagents. Each substitution mutant was tested for creatine transport activity and sensitivity to the following MTS reagents: 2-aminoethyl methanethiosulfonate (MTSEA), 2-(trimethylammonium) ethyl methanethiosulfonate (MTSET), and 2-sulfonatoethyl methanethiosulfonate (MTSES). Two mutants (G134C and Y148C) were inactive, but most mutants showed significant levels of creatine transport. Treatment with MTSEA inhibited the activity of the W154C, Y147C, and I140C mutants. Creatine partially protected I140C from inactivation, and this residue, like Cys-144 in the wild-type CreaT, is predicted to be close to a creatine binding site. MTSEA inactivation of Y147C was dependent on Na Creatine is present at high concentrations in tissues with large and fluctuating demands for energy such as heart, skeletal muscle, and brain. Creatine is converted to phosphocreatine by creatine kinase following ATP synthesis in mitochondria. Phosphocreatine is used to recycle ATP by reversal of this reaction at sites of high energy utilization. In mammals creatine is either obtained by synthesis from sequential reactions occurring in the kidney and liver or from the diet. Interestingly, tissues that contain high levels of creatine/phosphocreatine do not appear to synthesize their own creatine (1). A specific uptake system for creatine was first identified in skeletal muscle (2) and later shown to be present in various cultured cell preparations (3, 4) as well as human monocytes and macrophages (5).Molecular cloning studies identified muscle and brain cDNAs encoding a high affinity Na ϩ -and Cl Ϫ -dependent creatine transporter (6).Rabbit CreaT 2 exhibited significant homology to the GABA and norepinephrine transporters (7,8) and other members of the Na ϩ -and Cl Ϫ -dependent neurotransmitter (9, 10) or solute carrier 6 (SLC6) family of transporters (11). The SLC6 family includes solute transporters for dopamine, serotonin, glycine, taurine, proline, betaine, a system B 0ϩ cationic and neutral amino acid transporter (11), and a system B 0 neutral amino acid transporter mutated in Hartnup disorder (12, 13). The Na ϩ -and Cl Ϫ -dependent creatine transporter (SLC6A8) has been shown recently to be responsible for the absorption of creatine by intestinal epithelia (14) and transport of creatine across the blood-brain and blood-retina barriers (15,16). Mutations in the SLC6A8 gene result in the absence of creatine in the brain and a novel form of X-linked mental retardation. This is characterized by expressive speech and language delays, epilepsy, developmental delay, and autistic behavior (17, 18). All members of the SLC6 family of transporters are predicted to consist of 12 membrane-spanning domains, a large extracellular loop between the third and fourth transmembrane domains ...

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“…This change was first noted during recirculation; ische mia of itself did not alter the size of the total cre atine pool. Uptake of creatine has been shown to be dependent on a transmembrane Na + gradient in brain slices and cultured cells of other tissues, and the process is inhibited by ouabain (Gonda and Quastel, 1962;Daly and Seifter, 1980). Reperfusion, although thought to have been inadequate for op timal metabolic recovery in these subcortical re gions, may nonetheless have enabled vascular washout of diffusible creatine, causing the decrease in the total creatine pool.…”

Section: Discussionmentioning

confidence: 99%

Regional Brain Energy Metabolism after Complete versus Incomplete Ischemia in the Rat in the Absence of Severe Lactic Acidosis

Yoshida

Busto

Martinez

et al. 1985

J Cereb Blood Flow Metab

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Summary: Levels of energy metabolites were measured in forebrain regions in fasted rats subjected to 4-h recir culation after 1 h of either incomplete or complete ische mia. Both models of ischemia were produced by a pro cedure combining bilateral common carotid artery occlu sion, systemic hypotension, and CSF pressure clevation; the degree of intracranial hypertension was varied to pro duce incomplete and complete ischemia. Levels of brain lactate at the end of ischemia ranged from 16 to 19 mmoll kg in incomplete ischemia and from 11 to 13 mmollkg in complete ischemia. Energy metabolism recovered evenly in the neocortical and subcortical regions with recircu lation after incomplete ischemia. The metabolic recovery in the cerebral cortex after complete ischemia was similar to that observed after incomplete ischemia; however, reSevere tissue lactic acidosis (i.e., lactate concen tration > 20 mmollkg) has been shown to worsen brain damage in cerebral ischemia. Evidence for this includes studies of the recovery of neurological function (Myers and Yamaguchi, 1977;Siemkowicz and Hansen, 1978), recovery of CBP and brain en ergy metabolism (Ginsberg et aI., 1980; Welsh et aI., 1980), and histopathology (Kalimo et aI. , 1981; Pulsinelli et aI., 1982). The relative effects of com plete versus incomplete cerebral ischemia on the postischemic recovery of a variety of parameters have been the subject of several reports. Although it was generally assumed that complete ischemia is more harmful to the brain than incomplete ische-

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Uptake of creatine by cultured cells

Cited by 66 publications

References 16 publications

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

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

Substituted Cysteine Accessibility of the Third Transmembrane Domain of the Creatine Transporter

Regional Brain Energy Metabolism after Complete versus Incomplete Ischemia in the Rat in the Absence of Severe Lactic Acidosis

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