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Query: UNIPROT:P06889 (Mol)
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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 in vivo dose-response relationship between toluene and reactive oxygen species (ROS) formation in rat brain, liver, kidney, and lung, and the time-course of these effects has been characterized. The rate of oxygen radical formation was measured using the probe 2',7'-dichlorofluorescin diacetate. In vivo exposure to various doses of toluene (0.5, 1.0, and 1.5 g/kg ip) elicited a dose-dependent elevation of ROS generation within crude mitochondrial fractions obtained from rat lung and kidney, and within crude synaptosomal fractions from cerebellum. ROS formation in crude mitochondrial fractions from liver, and crude synaptosomal fractions from striatum and hippocampus, reached a maximum value at relatively low doses of toluene. Of the brain regions, the hippocampus had the highest induced levels of ROS. In vivo exposure to a single dose of toluene (1.5 g/kg ip), revealed that toluene-induced ROS reached a peak within 2 h, which correlated directly with measured toluene blood levels. This elevated oxidative activity was maintained throughout the next 24 h, even though blood values of toluene decreased to negligible amounts. These results demonstrate that exposure to toluene results in broad systemic elevation in the normal rate of oxygen radical generation, with such effects persisting in the tissues despite a rapid decline in toluene blood levels. Acute exposure to toluene may lead to extended ROS-related changes, and this may account for some of the clinical observations made in chronic toluene abusers.
Mol Chem Neuropathol 1993 Apr
PMID:Toluene-induced oxidative stress in several brain regions and other organs. 850 7

The inoculation of pea endocarp tissue with the bean pathogen Fusarium solani f. sp. phaseoli results in a non-host resistance response causing a complete cessation of fungal growth within 6 to 8 h. In addition to previously reported elicitation by chitosan, we now report that components of this response are also induced by a DNase released from this fungus. A single band of protein corresponding with DNase activity elicits phytoalexin production and the accumulation of RnA homologous with the pathogenesis-related (PR) genes DRR49, DRR206, and DRR230. Both the enzyme activity and the eliciting potential of the Fusarium DNase (Fsp DNase) are heat stable but susceptible to digestion by proteinase K. Fsp DNase mimics the intact fungus in inducing resistance against F. solani f. sp. pisi. Also, Fsp DNase causes similar cytologically detectable changes in pea tissue, such as increasing hypersensitive discoloration and diminishing fluorescence of Hoechst 33342-stained nuclei and fluorescein diacetate stained cells.
Mol Plant Microbe Interact
PMID:Fusarium solani DNase is a signal for increasing expression of nonhost disease resistance response genes, hypersensitivity, and pisatin production. 866 96

Gallbladder cell cultures obtained from rabbits subjected to sham or 72 h of bile duct ligation (72 h BDL, cholecystitis model) were incubated with calcium ionophore (A23187), dibutyryl cAMP (cAMP), and phorbol 12,13-diacetate (phorbol) to determine the intracellular signal transduction mechanisms responsible for increased inflamed gallbladder eicosanoid synthesis. Incubation of sham and 72 h BDL cell cultures with A23187 or phorbol significantly increased, whereas cAMP decreased, release of 6-keto-PGF1 alpha, PGE2, thromboxane B2 (measured by enzyme immunoassay) in a dose-related manner. Seventy-two-hour BDL cell cultures contained a specific 2-fold increased level of prostacyclin synthase compared to sham cell cultures which was not altered by preincubation with A23187, phorbol or cAMP. These findings suggest that increased PGI2 release in the sham and inflamed cell cultures following A23187 and phorbol stimulation was mediated in part via the inositol triphosphate pathway and protein kinase C activation and was not associated with altered cyclooxygenase or prostacyclin synthase content.
Mol Cell Endocrinol 1995 Nov 30
PMID:Regulation of eicosanoid synthesis in fibroblasts from inflamed gallbladders. 867 62

To elucidate that in iron-catalyzed oxidative damage the interaction of iron complex with the target molecules is important, the oxidative damage to plasmid DNA, protein and fatty acid has been compared using iron-chelate complexes with nitrilotriacetic acid (nta), citric acid, ethylenediamine-N,N'-diacetic acid (edda) and diethylenetriamine-N,N,N',N",N"-pentaacetic acid (dtpa). In the presence of hydrogen peroxide, plasmid pBR322 strand breaks occurred in the order of Fe-edda > Fe-citrate > Fe-nta > > Fe-dtpa. However, fragmentation of bovine serum albumin and diene conjugation of linoleic acid micelle occurred in the order of Fe-nta > Fe-edda > > Fe-citrate > Fe-dtpa = O, which were similar to hydroxyl radical production by these iron complexes and H2O2. Bleomycin-detectable free radical-promoting irons in these iron complexes were about 85% of iron in Fe-nta, Fe-citrate and Fe-edda, and only about 33% in Fe-dtpa. Not only hydroxyl radical productivity and free radical-promoting iron content in iron complex, but also the interaction of the complex with the target molecules determines the iron-catalyzed oxidative damage.
Biochem Mol Biol Int 1996 May
PMID:Oxidative damages by iron-chelate complexes depend on the interaction with the target molecules. 879 30

In fed and starved carp, Cyprinus carpio, ketone body metabolism and those metabolic and endocrine factors that are known to induce ketogenesis in starving mammals were investigated. Acetoacetate was detected in plasma and liver of both fed and starved carp. We could not detect 3-hydroxybutyrate, neither by 1H-NMR spectroscopy nor by spectrophotometric assay, in spite of low activities of hepatic 3-hydroxybutyrate dehydrogenase. Starvation of carp did not create metabolic conditions that would favor ketone body synthesis: Mobilization and hepatic catabolism of fatty acids were only moderately enhanced, the rate of gluconeogenesis was not elevated, and glucagon levels as well as the glucagon/insulin-ratio remained stable or declined. Therefore, the discrepancy in the effect of food deprivation on mammalian and teleostean ketogenesis appears to be caused not by the absence of the ketogenic pathway from teleosts but by major differences between mammals and fish in their metabolic response to starvation.
Comp Biochem Physiol B Biochem Mol Biol 1997 Feb
PMID:Ketone body metabolism in the Carp Cyprinus carpio: biochemical and 1H NMR spectroscopical analysis. 915 88

Leishmania promastigotes respond to hypotonic challenges by a mechanism of regulatory volume decrease (RVD), whereby anionic amino acid channels (HAAC) are hypotonically-activated and intracellular amino acids are released from the cells. Irrespective of the experimental conditions, restoration of isotonicity triggered an immediate blockage of the amino acid release. Both the speed and amplitude of the response depended on the hypotonic stimulus and on the operation of intracellular signaling mechanisms. The initial (5 s) hypotonic-induced release of amino acids (ri) and the steady state levels of amino acids attained (5 min) or amplitude (A), were markedly affected by modulators of protein kinase C: phorbol 12-myristate 13-acetate, 1-oleoyl-2-acetylglycerol and phorbol 12,13-diacetate whereas staurosporine and the related analog, bis-indolylmaleimide I (GF-109203.X) inhibited the RVD response. Agonists of cAMP-dependent protein kinase A such as forskolin or (8-(4-chlorophenylthio))-adenosine-3',5'cyclic-monophosphate enhanced the speed of the response but had little effect on its amplitude. Neither 4alpha-phorbol 12,13-didecanoate,1,9-dideoxyforskolin nor genistein, tamoxifen or thapsigargin had any apparent effect on either parameter tested. The most striking stimulation of hypotonic-induced amino acid release was exerted by arachidonic acid or by its non-metabolizable analog, 5,8,11,14-eicosatetraynoic acid (ETYA). These agents caused a major increase in the initial rate of amino acid release as well as a higher amplitude of the response, both of which were markedly inhibited by an anion channel blocker. The present studies indicate not only that hypotonicity is an obligatory and dominant component in HAAC activation, but implicate specific second messengers in the modulation of the RVD response. The modes of activation or attenuation of HAAC activity apparently differ for PKC and PKA modulators as well as for arachidonic acid. The involvement of Ca2+ in HAAC was studied in hypotonic challenged cells which were treated with intracellular Ca2+-chelators or Ca2+-free medium. These cells showed a lag in AA release and a modest inhibition of the amplitude. The inhibition of HAAC was markedly increased when cells were treated with the ionophore A23187 in Ca2+-free media. The HAAC activity was accompanied by a significant increase in internal Ca2+ when performed in Ca2+-containing medium (from 88+/-9 to 179+/-22 nM) but by no significant change when measured in Ca2+-free medium. These studies indicate that although Ca2+ might be involved in the early activation phase of HAAC, it is either not absolutely required or its action might be associated with localized events.
Mol Biochem Parasitol 1997 Dec 15
PMID:Modulation of the swelling-activated amino acid channel of Leishmania major promastigotes by protein kinases. 947 93

Insulin has pleiotropic effects on the regulation of cellular growth, differentiation, and metabolism. The biochemical events ultimately leading to cell proliferation after insulin treatment have been demonstrated in detail by numerous research groups. However, depending on cell types, it has been shown that insulin has various effects on cell proliferation. Therefore, we attempted to more critically evaluate the effect of insulin on cell proliferation in 3T3 L1 fibroblasts. In this study, we investigated insulin's effect on cell proliferation by using [3H]thymidine incorporation, flow cytometry, and cell counting. In 3T3 L1 fibroblasts studied in 0.5% serum, insulin induced a two-fold increase in [3H]thymidine incorporation over at 48 h, and the maximal rate of DNA synthesis was observed during 8-12 h incubation. The flow cytometric analysis also showed that insulin increased the cell population in the S phase. After insulin treatment for 48 h, cell numbers increased approximately 45% in comparison with 0.5% serum control. Cell division was found to occur only once in 60 h after staining 3T3 L1 fibroblasts with carboxyfluorescein diacetate succinimidyl ester (CFSE). Taken together, this data indicates that insulin stimulated the transit from the G0/G1 to S phase, progressed the cell cycle through the G2/M phase, and increased the cell number. However, under our experimental conditions, cells divided only once in 60 h in the presence of insulin.
Mol Cells 1997 Dec 31
PMID:Insulin has a limited effect on the cell cycle progression in 3T3 L1 fibroblasts. 950 15

We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 microM decreased cell growth by 14%, while at 45 microM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.
Mol Cell Biochem 1998 Oct
PMID:The compound 14-keto-stypodiol diacetate from the algae Stypopodium flabelliforme inhibits microtubules and cell proliferation in DU-145 human prostatic cells. 978 57

Extract from Scutellaria baicalensis Georgi Attenuates Oxidant Stress in Cardiomyocytes. Journal of Molecular and Cellular Cardiology (1999) 31, 1885-1895. Scutellaria baicalensis Georgi is a Chinese herbal medicine used to treat allergic and inflammatory diseases. The medicinal effects of S. baicalensis root may result, in part, from its constituent flavones reported to have antioxidant properties. Since oxidants play multiple roles in cells, we tested whether S. baicalensis could confer protection in a cardiomyocyte model of ischemia and reperfusion. The intracellular fluorescent probes 2',7'-dichlorofluorescin diacetate (DCFH-DA, sensitive to H(2)O(2) and hydroxyl radicals) and dihydroethidium (DHE, sensitive to superoxide) were used to assess intracellular reactive oxygen species (ROS), and propidium iodide (PI) was used to assess viability in cultured embryonic cardiomyocytes. S. baicalensis extract (SbE) quickly attenuated levels of oxidants generated during transient hypoxia and during exposure to the mitochondrial site III inhibitor antimycin A, as measured by DCFH oxidation or by DHE oxidation. These attenuated oxidant levels were associated with improved survival and function. Cell death after ischemia/reperfusion decreased from 47+/-3 % in untreated to 26+/-2 % in S. baicalensis treated cells (P<0.001). After antimycin A exposure, S. baicalensis decreased cell death from 49+/-6 % in untreated to 23+/-4 % in treated cells. Return of contraction occurred in S. baicalensis-treated cells but was not observed in control cells. Other in vitro studies revealed that baicalein, a major flavone component of SbE can directly scavenge superoxide, hydrogen peroxide, and hydroxyl radicals. Collectively, these findings indicate that SbE and its constituent flavones such as baicalein can attenuate oxidant stress and protect cells from lethal oxidant damage in an ischemia-reperfusion model.
J Mol Cell Cardiol 1999 Oct
PMID:Extract from Scutellaria baicalensis Georgi attenuates oxidant stress in cardiomyocytes. 1052 26


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