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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of a synthetic glucocorticoid (dexamethasone; Dex) on protoeolysis and on protease messenger RNA (mRNA) concentrations in rat L8 skeletal myotube cultures. Protein degradation was measured as release of radioactive trichloroacetic acid-soluble material from intracellular proteins pre-labelled with [3H]tyrosine. Dex (1 microM) stimulated protein degradation (P < 0.01). This effect was entirely blocked by the glucocorticoid antagonist, RU38486 (mifepristone; P < 0.01). Hence, actions of Dex on muscle protein degradation are mediated via intracellular glucocorticoid receptors. Molecular mechanisms by which glucocorticoids stimulate protein degradation in skeletal muscle are not known. Here, we investigated the regulation of protease (cathepsin B, cathepsin D, proteasome C2 subunit and m-calpain) mRNA concentrations by Dex in cultured L8 muscle cells. Cathepsin B mRNA concentration was enhanced 3.3-fold by Dex. This effect was blocked by RU38486. RU38486 alone did not affect cathepsin B mRNA concentration or mRNAs of other proteases. Concentrations of cathepsin D and m-calpain mRNAs were also increased by Dex. These effects were also abolished by RU38486. Proteasome C2 mRNA was unaffected by Dex and Dex reduced alpha-tubulin mRNA. Thus, glucocorticoids specifically regulate the concentrations of mRNAs encoding some proteases in muscle cells. The regulation of protease mRNA concentration is mediated via interaction between Dex with glucocorticoid receptors and is independent of the actions of Dex on mRNA encoding house-keeping proteins. These changes may underlie glucocorticoid-dependent control of proteolysis in muscle.
Mol Cell Endocrinol 1995 Feb 27
PMID:Effects of dexamethasone on protein degradation and protease gene expression in rat L8 myotube cultures. 775 36

The involvement of continuous protein synthesis in the mechanisms of crustacean steroidogenesis was investigated using crayfish molting glands (Y-organs). During intermolt, Y-organ steroidogenic activity is low. Eyestalk ablation initiates premolt which is characterized by a rapid increase in the production of ecdysteroids. In vitro incorporation of [14C]leucine into TCA-precipitable proteins was measured in Y-organs. A significant increase of de novo protein synthesis within 2 h and simultaneously led to a strong inhibition of the ecdysteroid synthesis. Sinus gland extracts (containing molt inhibiting hormone) also induced both a limited but reproducible inhibition of Y-organ protein synthesis and a pronounced inhibition of ecdysteroid production within 2 h. The results suggest a functional link between protein synthesis in the Y-organ and sustained ecdysteroid production. The analysis of autoradiographs from one-dimensional gel electrophoreses revealed an overall increase in de novo synthesis of glandular proteins in early premolt but also a more specific effect on distinct proteins (increase of 150, 140, 50-60, 22 and 15-18 kDa proteins) which may be more directly involved in the regulation of ecdysteroidogenesis.
Mol Cell Endocrinol 1995 Mar
PMID:Regulation of steroidogenesis in crayfish molting glands: involvement of protein synthesis. 778 20

Metabolic characteristics of experimental hepatoma cells include elevated rates of glycolysis and lipid synthesis. However, pyruvate derived from glucose is not redily oxidized, and the source of acetyl CoA for lipid synthesis in As-39D cells has not been characterized. In this study ketone bodies were examined as a possible source of acetyl CoA in AS-30D hepatoma cells. The major findings were: 1. Acetoacetate was utilized by AS-30D cells, with 14C-lipid and 14CO2 as major products of [3-14C] acetoacetate. 2. Lipid synthesis from acetoacetate was dependent on the presence of glucose in the medium. 3. Acetoacetate supported rapid respiration by AS-30D mitochondria in the presence of 0.1 mM malate. 4. Succinyl CoA acetoacetyl CoA transferase activity in AS-30D mitochondria was approximately 40 fold greater than that found in rat liver mitochondria. 5. Addition of acetoacetate, but not beta-hydroxybutyrate decreased conversion of [1-14C] acetate to 14CO2, presumably by diluting the specific radioactivity of the acetyl CoA derived from the acetate tracer. 6. In the presence of glucose, approximately one fourth of acetoacetate utilized was converted to lipid. This result is consistent with elevated lipogenesis postulated by the truncated TCA cycle hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Jul 27
PMID:Acetoacetate metabolism in AS-30D hepatoma cells. 784 66

The promoter of the human granulocyte-macrophage colony-stimulating factor gene is regulated by an inducible upstream enhancer. The enhancer encompasses three previously defined binding sites for the transcription factor NFAT (GM170, GM330, and GM550) and a novel NFAT site defined here as the GM420 element. While there was considerable redundancy within the enhancer, the GM330, GM420, and GM550 motifs each functioned efficiently in isolation as enhancer elements and bound NFATp and AP-1 in a highly cooperative fashion. These three NFAT sites closely resembled the distal interleukin-2 NFAT site, and methylation interference assays further defined GGA(N)9TCA as a minimum consensus sequence for this family of NFAT sites. By contrast, the GM170 site, which also had conserved GGA and TCA motifs but in which these motifs were separated by 15 bases, supported strong independent but no cooperative binding of AP-1 and NFATp, and this site functioned poorly as an enhancer element. While both the GM330 and GM420 elements were closely associated with the inducible DNase I-hypersensitive site within the enhancer, the GM420 element was the only NFAT site located within a 160-bp HincII-BalI fragment defined by deletion analysis as the essential core of the enhancer. The GM420 element was unusual, however, in containing a high-affinity NFATp/c-binding sequence (TGGAAAGA) immediately upstream of the sequence TGACATCA which more closely resembled a cyclic AMP response-like element than an AP-1 site. We suggest that the cooperative binding of NFATp/c and AP-1 requires a particular spacing of sites and that their cooperativity and induction via independent pathways ensure very tight regulation of the granulocyte-macrophage colony-stimulating factor enhancer.
Mol Cell Biol 1995 Apr
PMID:Human granulocyte-macrophage colony-stimulating factor enhancer function is associated with cooperative interactions between AP-1 and NFATp/c. 789 2

The bloodstream forms of the protozoan parasite Trypanosoma brucei lack spectrally detectable cytochromes and satisfy energy requirements mainly by glycolysis. When infected blood is ingested by the tse-tse fly vector, the bloodstream form cells differentiate to procyclic forms that have fully functional mitochondria. Procyclic cells have cyanide-sensitive, cytochrome-mediated electron transport and the full complement of TCA cycle enzymes. The developmental regulation of the cytochrome c reductase complex was examined at the RNA and protein levels. RNase T1 protection studies and Northern blot analyses demonstrated that bloodstream and procyclic form cells constitutively expressed the genes for two nuclear encoded cytochrome c reductase subunits, cytochrome c1 and subunit 4. Polyadenylated transcripts of both genes were present in bloodstream form cells at up to 20% of the procyclic cell levels. These levels were significantly up-regulated sometime after the onset of differentiation to the procyclic form. Despite the presence of subunit mRNAs in bloodstream form cells, subunit proteins were not detected until the cells had been allowed to differentiate in vitro for 6 h. Procyclic cell levels of subunit proteins and holocytochromes were reached by 48 h. Our results suggest that cytochrome c reductase is developmentally regulated at multiple levels, some involving post-transcriptional mechanisms.
Mol Biochem Parasitol 1994 Jun
PMID:Developmental regulation of Trypanosoma brucei cytochrome c reductase during bloodstream to procyclic differentiation. 796 70

Tetrathiomolybdate (TTM) was injected at a dose of 10 mg/kg bw daily for eight consecutive days into Long-Evans Cinnamon (LEC) rats, which inherently abnormally deposit Cu (260 micrograms/g) in the liver. The hepatic Cu (100 micrograms/g) and metallothionein (MT) bound Cu (from 2,600 to 540 micrograms/g protein) concentrations were decreased greatly by the injection. On the other hand, the renal Cu concentration increased significantly, but the brain Cu concentration only very slightly. The reduction of the hepatic Cu concentration was accompanied by reductions of Zn and Fe concentrations in the liver, kidney and brain. The TTM compound slightly stimulated excretion (about 3-fold) of Cu into the bile, but greatly (about 40-fold) into the blood. In rats not treated with TTM, most biliary (100%) and serum (78%) Cu was recovered in the trichloroacetic acid (TCA) soluble fraction. On the other hand, in rats treated with TTM, bile and serum Cu were recovered overwhelmingly in the TCA insoluble fraction, probably in the form of a Cu-TTM-albumin complex. Our results suggest that although there is an inherent failure in the intrinsic secretory process of Cu from the liver in LEC rats, the TTM compound can remove Cu from Cu-MT, resulting in a decrease of hepatic Cu.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Removal of copper from the liver of Long-Evans Cinnamon (LEC) rats by tetrathiomolybdate (TTM) injection: the main excretion route is via blood, not bile. 799 66

The present studies examined how 125I-labeled basic fibroblast growth factor (bFGF) bound to high affinity receptors and with lower affinity to heparan sulfate proteoglycans (HSPG) of cultured immature rat Leydig cells was processed. Following incubation for 2 h at 4 degrees C with 125I-bFGF, cells were washed to remove unbound radioactivity. Fresh medium was added, and cells were incubated at 4 degrees and/or 37 degrees C. At time zero and at specific intervals over the next 6 h, the incubation medium was saved and cells washed to quantitate 125I-bFGF released into the medium, associated with HSPG of the cell surface or extracellular matrix (radioactivity released by washing cells with 2 M NaCl, pH 7.4), associated with cell surface receptors (radioactivity released by washing cells with 2 M NaCl, pH 4.0) or internalized (radioactivity resistant to high salt and acid washes, and solubilized with 0.5 M NaOH). Radioactivity released into the initial medium and the pooled washes was further divided into a trichloroacetic acid (TCA)-precipitated form (radioactivity precipitated by 10% TCA) and a TCA-soluble form (radioactivity remaining in the TCA supernatant). 125I-bFGF associated with both HSPG and surface receptors declined progressively during the first 4 h of incubation before stabilizing when cells were transferred to 37 degrees C. These declines were associated with a corresponding increase in intracellular 125I-bFGF. These changes were blocked by maintaining cells at 4 degrees C. The majority of internalized 125I-bFGF appeared to originate from the HSPG-bound fraction as there was a greater decline in HSPG-associated radioactivity and most of the increase in internalized radioactivity could be blocked by the inclusion of 10 micrograms/ml heparin (which mainly blocks 125I-bFGF binding to HSPG but not to high affinity receptors) during the initial incubation with 125I-bFGF for 2 h at 4 degrees C. Furthermore, HSPG-mediated internalization appeared to have two components: the major fraction was blocked by the inclusion of 10 micrograms/ml heparin, while a heparin-resistant fraction, appeared to be closely linked both quantitatively and temporarily to receptor-mediated internalization. A minor fraction of internalized 125I-bFGF was metabolized in lysosomes, as the inclusion of 50 microM chloroquine during the 6 h incubation at 37 degrees C inhibited most of the increase in TCA-soluble radioactivity appearing in the incubation medium.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Endocrinol 1993 Dec
PMID:Evidence that both receptor- and heparan sulfate proteoglycan-bound basic fibroblast growth factor are internalized by cultured immature Leydig cells. 814 17

Major non-coding region of human mitochondrial DNA (mtDNA) (1122 bp) was assessed using the method of complexity analysis of genomes. The ACT, TCA, AGT and TGA motifs (AST-repeats) were shown to form short repeats as well as more complex block structures. These motifs are intrinsic for regulatory sequences of DNA of procaryotic and eucaryotic genes. ACT-repeats based blocks happen to be the most variable parts of the region studied too. Each inherited type of mtDNA is proposed to be a pattern of short repeats arranged with the regard to their symmetry, complementarity and alternativeness thus forming block DNA structures. The existence of similar structures may be possible due to the variability of nucleotide sequences more pronounced in the blocks of repeats of major non-coding region of human mtDNA.
Mol Biol (Mosk)
PMID:[Short repeats and variability in the smooth noncoding area of human mitochondrial DNA]. 824 30

A causative factor in the development of diabetes-induced heart dysfunction may be abnormalities in myocardial energy metabolism. Using 13C-NMR spectroscopy, we investigated the effects of experimentally induced diabetes (streptozotocin 65 mg/kg, i.v.) on glucose metabolism and contractile function in the isolated perfused rat heart. Hearts from streptozotocin-treated and untreated control rats were perfused with 11 mM [1-13C]glucose as substrate and 1H-decoupled 13C-spectra recorded for up to 90 min. Incorporation of label from [1-13C]glucose into lactate and glutamate was observed in hearts from control animals, consistent with metabolism through glycolysis and TCA cycle, respectively. Diabetic hearts did not incorporate label into lactate or glutamate. Addition of insulin (0.05 U/ml) to the buffer resulted in the appearance of [3-13C]lactate, although glutamate labeling was not observed. Addition of insulin plus dichloroacetate (2 mM) resulted in incorporation of label from [1-13C]glucose into 2-, 3- and 4-13C-glutamate, indicating glucose entry into the TCA cycle. Addition of insulin, or insulin plus dichloroacetate to control hearts did not alter labeling of either lactate or glutamate. Cardiac function in hearts from the diabetic group was depressed compared to controls and declined significantly over the duration of the experiment. These studies show that concomitant with a decrease in cardiac function, glucose oxidation is profoundly inhibited following the induction of diabetes with streptozotocin. These observations are consistent with a combination of decreased glucose transport and a decrease in pyruvate dehydrogenase activity.
J Mol Cell Cardiol 1993 Oct
PMID:A 13C-NMR study of glucose oxidation in the intact functioning rat heart following diabetes-induced cardiomyopathy. 826 54

In this study the trichloroethylene treatment-associated production of oxidative stress in mouse liver by measurements of changes in oxygen consumption, the disappearance of beta-nicotinamide adenine dinucleotide reduced form (NADPH), and the rate of malondialdehyde formation have been investigated. The treatment of mice with trichloroethylene (TCE), trichloroacetic acid (TCA), a metabolite of TCE, or clofibrate, a peroxisome proliferator, resulted in an increase in the oxygen consumption of liver microsomes compared to the values of the untreated controls. A maximum increase in the level of oxygen consumption in liver microsomes was observed in the mice treated with TCE, followed by clofibrate and TCA treatments. All three agents also increased the rate of NADPH oxidation in mice liver microsomes compared with untreated controls. NADPH oxidation was increased four fold by TCE or clofibrate (38 or 37 nmol/min) and two fold by TCA treatment (17 nmol/min) over that of the control animals (9 nmol/min). The concentration of malondialdehyde was higher in all three treated groups in comparison with control values. Malondialdehyde levels were elevated by 227%, 191%, and 118% by treatment with TCE, clofibrate, and TCA, respectively. Increases in the levels of oxygen consumption, NADPH disappearance, and malondialdehyde production in microsomes from liver of mice treated chronically with TCE or TCA are all indicative of elevated levels of oxidative stress. Increased oxidative stress may be involved in the induction of TCE-associated hepatotoxicity.
Biochem Mol Biol Int 1993 Oct
PMID:Increased oxidative stress in the liver of mice treated with trichloroethylene. 827 17


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