Maturational increase in mouse brain creatine kinase reaction rates shown by phosphorus magnetic resonance

Holtzman, David; McFarland, Eric W.; Jacobs, Danny O.; Offutt, Martin; Neuringer, L. J.

doi:10.1016/0165-3806(91)90004-3

Cited by 46 publications

(46 citation statements)

References 31 publications

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“…These differences between gray and white matter are the same as those seen in piglets and rats [4,5]. The maturational increases in whole brain CK-catalyzed reaction rate constants and CK isoenzymes are larger in the mouse and rat than in the rabbit, but occur at the same ages [4,14]. This is the first study of the CrT in the developing brain.…”

Section: Discussionsupporting

confidence: 65%

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Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Kekelidze

Khait²,

Togliatti³

et al. 2000

Dev Neurosci

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Systemic creatine (Cr) supplementation increases brain phosphocreatine (PCr) and prevents hypoxic seizures in 15-day-old rabbits . Between 5 and 30 days of age during normal development, rabbit gray matter mitochondrial creatine kinase (Mi-CK) increases 400% while cytosolic CK (BB-CK) increases 60%. In white matter, both isoenzymes show smaller, similar increases (40%) during this period. The Cr transporter protein decreases 60% between 5 and 15 days in both regions. In vivo CK rate constants measured by ³¹P nuclear magnetic resonance increase 30% between 10 and 20 days, and then fall 50% between 20 and 30 days in predominantly gray matter slices. Similar maturational changes are seen in predominantly white matter slices. Injecting Cr at 15 days does not significantly change BB-CK or Mi-CK isoenzymes or the in vivo CK reaction rate constants. Thus, the largest change in the CK system associated with suppression of hypoxic seizures in Cr-treated rabbits is increased PCr in gray and white matter.

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Section: Discussionsupporting

confidence: 65%

“…Use of this model does not imply that the reaction is first order. Only the forward rate constant is measured in these studies, but the CK reaction rates in the rat brain are equal in the two directions when reactant concentrations are stable [14].…”

Section: Nmr Experimentsmentioning

confidence: 99%

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Kekelidze

Khait²,

Togliatti³

et al. 2000

Dev Neurosci

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“…We also measured equal fluxes in CK-Comb livers expressing both CK isoenzymes. Reversible P i transfer at equal rates was demonstrated in vitro (46), with ex vivo stimulation of slow twitch muscle (22) and in vivo during a maturational increase in CK activity in the mouse brain (14). However, other in vivo studies have reported V for -to-V rev ratios of 2-2.4 in tissues with variable composition of CK isoenzymes, including brain, heart, and skeletal muscle (5,26,39,45).…”

Section: Discussionmentioning

confidence: 91%

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

Askenasy

Koretsky

2002

American Journal of Physiology-Cell Physiology

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Askenasy, Nadir, and Alan P. Koretsky. Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels. Am J Physiol Cell Physiol 282: C338-C346, 2002. First published October 3, 2001 10.1152/ajpcell.00404.2001.-The function of creatine kinase (CK) and its effect on phosphorus metabolites was studied in livers of transgenic mice expressing human ubiquitous mitochondrial CK (CK-Mit) and rat brain CK (CK-B) isoenzymes and their combination.31 P NMR spectroscopy and saturation transfer were recorded in livers of anesthetized mice to measure high-energy phosphates and hepatic CK activity. CK reaction velocity was related to total enzyme activity irrespective of the isoenzyme expressed, and it increased with increasing concentrations of creatine (Cr). The fluxes mediated by both isoenzymes in both directions (phosphocreatine or ATP synthesis) were equal. Over a 20-fold increase in CK-Mit activity (28-560 mol ⅐ g wet wt Ϫ1 ⅐ min Ϫ1 ), the fraction of phosphorylated Cr increased 1.6-fold. Hepatic free ADP concentrations calculated by assuming equilibrium of the CK-catalyzed reaction in vivo decreased from 84 Ϯ 9 to 38 Ϯ 4 nmol/g wet wt. Calculated free ADP levels in mice expressing high levels of CK-B (920-1,635 mol ⅐ g wet wt Ϫ1 ⅐ min Ϫ1 ) were 52 Ϯ 6 nmol/g wet wt. Mice expressing both isoenzymes had calculated free ADP levels of 36 Ϯ 4 nmol/g wet wt. These findings indicate that CK-Mit catalyzes its reaction equally well in both directions and can lower hepatic apparent free ADP concentrations. mitochondrial creatine kinase; cytosolic creatine kinase; phosphorus-31 nuclear magnetic resonance spectroscopy; magnetization transfer; liver adenosine 5Ј-diphosphate concentration

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“…Thyroid hormone is known to regulate CK activity in muscle cells (76). Brain CK activity increases during development (77), and several lines of evidence suggest that brain-type CK is involved in the energetics of neurotransmitter release, restoration of ion gradients following membrane depolarization and axonal transport (78 -82).…”

Section: Identification Of T 3 -Regulated Neuralmentioning

confidence: 99%

Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

Denver

Pavgi

Shi

1997

Journal of Biological Chemistry

126

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Although thyroid hormone (TH) plays a significant role in vertebrate neural development, the molecular basis of TH action on the brain is poorly understood. Using polymerase chain reaction-based subtractive hybridization we isolated 34 cDNAs for TH-regulated genes in the diencephalon of Xenopus tadpoles. Northern blots verified that the mRNAs are regulated by TH and are expressed during metamorphosis. Kinetic analyses showed that most of the genes are up-regulated by TH within 4 -8 h and 13 are regulated by TH only in the brain. All cDNA fragments were sequenced and the identities of seven were determined through homology with known genes; an additional five TH-regulated genes were identified by hybridization with known cDNA clones. These include five transcription factors (including two members of the steroid receptor superfamily), a TH-converting deiodinase, two metabolic enzymes, a protein disulfide isomerase-like protein that may bind TH, a neural-specific cytoskeletal protein, and two hypophysiotropic neuropeptides. This is the first successful attempt to isolate a large number of TH-target genes in the developing vertebrate brain. The gene identities allow predictions about the gene regulatory networks underlying TH action on the brain, and the cloned cDNAs provide tools for understanding the basic molecular mechanisms underlying neural cell differentiation.

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Maturational increase in mouse brain creatine kinase reaction rates shown by phosphorus magnetic resonance

Cited by 46 publications

References 31 publications

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Brain Creatine Kinase and Creatine Transporter Proteins in Normal and Creatine-Treated Rabbit Pups

Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels

Thyroid Hormone-dependent Gene Expression Program for Xenopus Neural Development

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