Comparison of turnover rates of proteins of the brain, liver and kidney in mouse in vivo following long term labeling

Lajtha, Ábel; Latzkovits, L.; Tóth, Jenő

doi:10.1016/0005-2787(76)90015-0

Cited by 80 publications

(37 citation statements)

References 30 publications

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“…The present study utilized a continuous intravenous infusion of L- [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]leucine to investigate leucine metabolism in the near-term ovine fetal brain. This was accomplished with the measurement of tissue protein leucine specific activity, which reflects the unidirectional flux of leucine into cerebral protein, i.e., protein synthesis, and using Fick methodology to measure the uptake of labeled/unlabeled leucine by the brain, which reflects that utilized for protein synthesis/accretion, plus any leucine that is oxidized.…”

Section: Discussionmentioning

confidence: 99%

“…A-V differences were collected in both the LV/REM and HV/NREM behavioral states to determine the relationship between cerebral leucine metabolism and behavioral state activity during brain development. The label on L- [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]leucine at the carboxyl position can be measured in leucine that has been incorporated into protein, or it can be followed through the catabolic pathway, which involves the reversible transamination with ␣-ketoglutarate to form ␣-KIC, followed by oxidative decarboxylation to form 14 CO 2 , which diffuses out of the tissue (8). The measurement of tissue SA PB leucine along with that of the precursor pool at a defined time from the start of the tracer infusion provides a means of estimating the fractional synthetic rate of brain proteins, i.e., the percentage of brain proteins newly synthesized per unit time.…”

Section: Discussionmentioning

confidence: 99%

“…The infused labeled leucine will also be taken up by the brain and will equilibrate with the intracellular free leucine pool (25). However, depending on the half-life of proteins, which approximates 4 days for the adult brain (12), relative to the infusion time (6 h), there should be limited recycling of labeled leucine out of brain proteins due to degradation over the course of the study. Thus the measurement of labeled leucine uptake by the brain should mainly reflect that leucine directed toward protein synthesis as well as any that is oxidized.…”

Section: Discussionmentioning

confidence: 99%

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Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

Czikk

Sweeley

Homan

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state. Am J Physiol Regul Integr Comp Physiol 284: R200-R207, 2003; 10.1152/ ajpregu.00190.2002-Behavioral/sleep state activity may impact on synthetic processes within the brain, thus accounting for the developmental change in such activity and suggesting a role in the brain's growth and development. We have therefore determined the cerebral uptake of leucine and [ 14 C]leucine during continuous tracer infusion as measures of leucine metabolism in relation to behavioral state activity, as well as the regional flux of leucine into brain tissue in the ovine fetus near term. The cerebral fractional protein synthetic rate and the absolute protein synthetic rate averaged ϳ20%/day and ϳ1 g/day, respectively, as measured for the whole brain, which is considerably higher than anticipated protein accretion and indicates a high rate of protein turnover with protein synthesis closely linked to protein degradation. Measures of protein synthesis were significantly higher in the pituitary gland, which may be attributed to the active synthesis and export of peptide hormones from this region. Cerebral leucine and [14 C]leucine uptakes averaged ϳ630 and ϳ1,000 nmol ⅐ 100 g Ϫ1 ⅐ min Ϫ1 , with the latter higher than leucine unidirectional flux and thus supporting a degree of leucine oxidation by the brain. Cerebral leucine metabolism as studied was affected by behavioral state activity, with uptake measurements for both leucine and [ 14 C]leucine significantly increased during the high-voltage electrocortical/non-rapid eye movement state by 1.7-fold and 2.8-fold, respectively, indicating that protein synthesis and degradation must also be increased at this time, and supporting a role for behavioral state activity in the brain's growth and development. brain development; leucine metabolism CEREBRAL PROTEIN SYNTHESIS has been studied during brain growth and development, both pre-and postnatally in sheep (1, 24) and postnatally in the rat (6, 26), because proteins are integral components of structural elements in brain tissue and with the metabolism of brain protein directly related to maturational events (26). Initial study in the near-term ovine fetus by Schaefer and Krishnamurti (24) using a tyrosine isotopic-dilution technique showed high rates of cerebral protein synthesis with a fractional protein synthetic rate between 14 and 37%/day and an absolute rate of synthesis of ϳ1 g/day. A subsequent study in fetal sheep by Abrams and colleagues (1) using [14 C]leucine autoradiography reported a rate of leucine incorporation into brain protein of ϳ5 nmol ⅐ g Ϫ1 ⅐ min Ϫ1 , with an overall increase through the latter part of gestation and into the early postnatal period likely reflecting cerebral myelination. Postnatal studies in rats have similarly shown high rates of brain protein synthesis during early development, with peak values occurring shortly after birth and gradually decreasing thereafter (6, 26). While high rates of cerebral pr...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

Czikk

Sweeley

Homan

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Interestingly, different protein turnover rates have been observed in different tissues (74). For example, one study found slower protein turnover rates in the brain with an average lifetime of 9 days, whereas the average protein lifetime is 3 days in liver and 3.5 days in blood (75).…”

Section: Protein Turnovermentioning

confidence: 99%

The Regulation of Synaptic Protein Turnover

Álvarez-Castelao

2015

Journal of Biological Chemistry

100

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Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover, are tightly regulated, and are modulated by neuronal activity in time and space. The anisotropic anatomy of the neurons presents a challenge for the study of protein turnover, but the understanding of protein turnover in neurons and its modulation in response to activity can help us to unravel the fine-tuned changes that occur at synapses in response to activity. Here we review the key experimental evidence demonstrating the role of protein synthesis and degradation in synaptic plasticity, as well as the turnover rates of specific neuronal proteins.The human brain is composed of a trillion neurons with complex and intricate arbors, which are interconnected by synapses (1). Synapses are highly dynamic in number and shape as a consequence of the continuous remodeling of neural circuits. A change in synaptic transmission elicited by neural activity is collectively called "synaptic plasticity," and learning and memory rely, at least in part, on this process. Synapses are made up of proteins, including receptors for neurotransmitters, scaffolding molecules, and signaling molecules. All proteins have a finite lifetime: they are synthesized and degraded continuously to maintain cellular function and viability. This continuous process is called "protein turnover." However, why is protein turnover important for cells? Even when the cells are in a basal state, the protein pool is dynamic and the coordination between protein synthesis and degradation maintains a steady-state level of proteins that is constantly renewed (2). Protein turnover is not only important to maintain protein concentrations in the cell, but also to allow for changes. Modulation of the proteome is necessary for most cellular responses, involving modifications in general or specific protein turnover (3,4). Neurons also have the ability to modulate and adjust their proteome in response to specific cues, for example, synaptic remodeling in response to patterns of action potentials in neurons.One complication of protein turnover in neurons is that synapses can be located up to hundreds of microns from the cell body. Where are proteins synthesized and degraded? Are proteins transported over the long distance from the soma to dendrites or axons, and if so, how do they reach their specific location within the intricate axonal and dendritic arbors. In fact, to overcome these challenges, neurons have very effective transport mechanisms to deliver proteins to remote regions of axons or dendrites; this has been recently reviewed in Refs. 5 and 6. Moreover, some proteins, such as receptors or scaffolding proteins, are in continuous movement in and out of the synapse with rapid rates (reviewed in Refs. 7 and 8). In addition to protein movement, neurons use local translation and degradation in dendrites and axons, allowing for a fine-tuned local protein turnover. Here we present an overview focused on...

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“…In young, a single pool with a 2-day average half-life was found [Lajtha et al, 1976, The actual rate of amino acid incorporation was found to be about 0.7%/h in the adult; initially about half of the label is in the small, fast pool. In young, initial incorporation rates are 1.5-2.0%/h.…”

Section: Protein Biosynthesismentioning

confidence: 97%

Macromolecular Turnover in Brain during Aging

Stella

Lajtha

1987

Gerontology

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During aging there are several structural, functional and biochemical alterations, including changes in macromolecular composition and turnover. Regulation of gene expression, DNA and RNA synthesis, total poly(A)⁺ and poly(A)^–– RNA contents, qualitative and quantitative changes of synaptosomal plasma membrane proteins, diminished plasticity, loss of synapses, lower rate of axoplasmic transport, impairment of antioxidant and bioen-ergetic systems seem to be involved in the aging process of nervous system.

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Comparison of turnover rates of proteins of the brain, liver and kidney in mouse in vivo following long term labeling

Cited by 80 publications

References 30 publications

Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

The Regulation of Synaptic Protein Turnover

Macromolecular Turnover in Brain during Aging

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