Protein content of various regions of rat brain and adult and aging human brain

Banay‐Schwartz, M.; Kenessey, Ágnes; DeGuzman, T.; Lajtha, Ábel; Palkóvits, M.

doi:10.1007/bf02435024

Cited by 61 publications

(48 citation statements)

References 21 publications

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“…Alcohol dehydrogenase has been reported to have very low activity in the brain but appears to be heterogeneously distributed, occurring in some types of neurons (40,41). Cytochrome P450 also has been shown to metabolize Etoh in the brain in neurons and astroglia, depending on the brain regions (42), but at a rate of 0.00051 μmol/min/g (43), significantly more slowly than the rate of 0.012 μmol/min/g reported for catalase in brain homogenates (calculated from the 3.5-7.1 nmol/mg protein/h (11), using 0.1 g protein/g brain tissue (44)). Furthermore, inhibition of brain catalase activity in mice inhibits many of the pharmacologic effects of ethanol (45), and inhibition or stimulation of catalase activity in brain homogenates, respectively, reduces or increases the formation of AA (14,15).…”

Section: Discussionmentioning

confidence: 93%

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Wang

Jiang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague-Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-13 C]ethanol and [1, 2-13 C 2 ]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of 13 C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-naïve rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 μmol/min/g in astroglia and 0.014 ± 0.003 μmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 μmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-naïve rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for naïve and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. 13C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.T he liver is the major organ for the oxidation of ethanol (Etoh) (1, 2), followed by the stomach and other organs. Acetate (Ac) generated from Etoh by the liver is consumed by the brain (3, 4), where it replaces a significant portion of cerebral glucose metabolism in humans and animals (5-8), either decreasing glucose consumption directly or compensating for glucose consumption decreased by some other effect. However, the brain may also oxidize Etoh (9-14), and that capacity is important with respect to several perspectives. The first step of Etoh oxidation generates acetaldehyde (AA), which is toxic, reactive, and potentially carcinogenic. AA is aversive systemically, as has been observed from the unpleasant effects of disulfuram, an inhibitor of AA dehydrogenase, but it has been shown to be rewarding in parts of the brain (12,15,16) especially in the posterior ventral tegmental area (17-19) by activating dopamine neurons (20)(21)(22). The liver maintains circulating levels of AA at levels of 20-155 μM (23, 24), and AA has been reported not to penetrate the blood-brain barrier or to penetrate very slowly (23,25). Thus, if the brain can oxidize Etoh, then intracerebral AA may mediate behavioral, neurochemical, and toxic effects of Etoh in the brain, possibly playing a role in the development of alcohol dependence (6,16,26).AA is difficult to measure in living systems. The ...

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Section: Discussionmentioning

confidence: 93%

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Wang

Jiang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…GFAP represents about 1.0% of total brain protein in the adult rat (13). If brain is ϳ11% protein and 9% protein by wet weight in adult rat and human, respectively (14), or about 90 mg/ml, the GFAP concentration would be 0.90 mg/ml. If astrocytes take up about 10% of brain volume (15) and as GFAP is only found in astrocytes, the GFAP concentration in astrocytes is in the order of 9.0 mg/ml (may be higher in white matter astrocytes, as their GFAP content is greater than that of gray matter astrocytes).…”

Section: S Proteasome Bind To Assembled Gfap Filaments In Vitro-mentioning

confidence: 99%

Oligomers of Mutant Glial Fibrillary Acidic Protein (GFAP) Inhibit the Proteasome System in Alexander Disease Astrocytes, and the Small Heat Shock Protein αB-Crystallin Reverses the Inhibition

Tang

Perng

Wilk

et al. 2010

Journal of Biological Chemistry

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The accumulation of the intermediate filament protein, glial fibrillary acidic protein (GFAP), in astrocytes of Alexander disease (AxD) impairs proteasome function in astrocytes. We have explored the molecular mechanism that underlies the proteasome inhibition. We find that both assembled and unassembled wild type (wt) and R239C mutant GFAP protein interacts with the 20 S proteasome complex and that the R239C AxD mutation does not interfere with this interaction. However, the R239C GFAP accumulates to higher levels and forms more protein aggregates than wt protein. These aggregates bind components of the ubiquitin-proteasome system and, thus, may deplete the cytosolic stores of these proteins. We also find that the R239C GFAP has a greater inhibitory effect on proteasome system than wt GFAP. Using a ubiquitin-independent degradation assay in vitro, we observed that the proteasome cannot efficiently degrade unassembled R239C GFAP, and the interaction of R239C GFAP with proteasomes actually inhibits proteasomal protease activity. The small heat shock protein, ␣B-crystallin, which accumulates massively in AxD astrocytes, reverses the inhibitory effects of R239C GFAP on proteasome activity and promotes degradation of the mutant GFAP, apparently by shifting the size of the mutant protein from larger oligomers to smaller oligomers and monomers. These observations suggest that oligomeric forms of GFAP are particularly effective at inhibiting proteasome activity.Alexander disease (AxD) 2 is a rare but fatal disease of the central nervous system characterized by the presence in astrocytes of Rosenthal fibers, cytoplasmic protein aggregates that contain the intermediate filament protein, glial fibrillary acidic protein (GFAP), ubiquitinated proteins, and small heat shock proteins (shsps) (1). Because of the loss of myelin and oligodendrocytes and a variable loss of neurons, AxD has been historically thought of as a leukodystrophy or neurodegenerative disorder. AxD is, however, a disease of astrocyte dysfunction, as mutations in GFAP are found in the large majority of AxD patients (2). All mutations detected so far are heterozygous coding mutations, and most cases of AxD disease arise through de novo, dominant, GFAP mutations (2). Most of the AxD mutations reside in the 1A, 2A, and 2B segments of the conserved central rod domain of GFAP, but several are located in the tail region (2). Although GFAP mutations must underlie the pathogenesis of AxD, the mechanisms by which GFAP mutations are toxic have not been fully elucidated.The Arg-239 residue is a "hot spot" for GFAP mutagenesis, as substitutions at this arginine are the most frequent mutations found in AxD and appear among different ethnic groups (2). Our previous work has concentrated on the most common substitution, R239C, and has demonstrated that overexpressing GFAP, either wild type (wt) or the R239C mutant, leads to the formation of intracellular protein aggregates (3-5). GFAP accumulation also inhibited proteasome protease activity and increased levels of ubiquit...

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“…We identified two studies in which the affinity of rat TH for each of its three amino acid substrates was determined in vitro under the same conditions and in the presence of the natural cofactor tetrahydrobiopterin (Daubner et al, 1992;Fitzpatrick, 1991) (Table 2). Using brain tissue levels from our laboratory (Bongiovanni et al, 2010), reference values for protein and water content in rat brain (Banay-Schwartz et al, 1992;Schwab et al, 1997) and assuming homogeneous distribution in intracellular water, we estimated free intracellular amino acid levels (Table 3). The relative substrate affinities confirm that under usual conditions, brain TH would almost exclusively hydroxylate L-TYR rather than L-phenylalanine or L-tryptophan.…”

Section: Discussionmentioning

confidence: 99%

“… a cloned rat tyrosine hydroxylase (TH) expressed heterologously and assayed in presence of tetrahydrobiopterin (Daubner et al., 1992;Fitzpatrick, 1991), b average tissue levels in rat medial prefrontal cortex and striatum (Bongiovanni et al, 2010), c calculated for 122 mg/g protein (Banay-Schwartz et al, 1992), 78% water content (Schwab et al, 1997) in rat brain tissue and assuming homogeneous distribution of amino acids in intracellular water. …”

Section: Figurementioning

confidence: 99%

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat

et al. 2017

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We previously found that L-tyrosine (L-TYR) but not D-TYR administered by reverse dialysis elevated catecholamine synthesis in vivo in medial prefrontal cortex (MPFC) and striatum of the rat (Brodnik et al., 2012). We now report L-TYR effects on extracellular levels of catecholamines and their metabolites. In MPFC, reverse dialysis of L-TYR elevated in vivo levels of dihydroxyphenylacetic acid (DOPAC) (L-TYR 250 – 1000 μM), homovanillic acid (HVA) (L-TYR 1000 μM) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (L-TYR 500 – 1000 μM). In striatum L-TYR 250 μM elevated DOPAC. We also examined L-TYR effects on extracellular dopamine (DA) and norepinephrine (NE) levels during two 30 min pulses (P2 and P1) of K+ (37.5 mM) separated by t = 2.0 h. L-TYR significantly elevated the ratio P2/P1 for DA (L-TYR 125 μM) and NE (L-TYR 125 – 250 μM) in MPFC but lowered P2/P1 for DA (L-TYR 250 μM) in striatum. Finally, we measured DA levels in brain slices using ex-vivo voltammetry. Perfusion with L-TYR (12.5 – 50 μM) dose-dependently elevated stimulated DA levels in striatum. In all the above studies, D-TYR had no effect. We conclude that acute increases within the physiological range of L-TYR levels can increase catecholamine metabolism and efflux in MPFC and striatum. Chronically, such repeated increases in L-TYR availability could induce adaptive changes in catecholamine transmission while amplifying the metabolic cost of catecholamine synthesis and degradation. This has implications for neuropsychiatric conditions in which neurotoxicity and / or disordered L-TYR transport have been implicated.

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Protein content of various regions of rat brain and adult and aging human brain

Cited by 61 publications

References 21 publications

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Oligomers of Mutant Glial Fibrillary Acidic Protein (GFAP) Inhibit the Proteasome System in Alexander Disease Astrocytes, and the Small Heat Shock Protein αB-Crystallin Reverses the Inhibition

L-Tyrosine availability affects basal and stimulated catecholamine indices in prefrontal cortex and striatum of the rat

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