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91.
The stable isotope-based dynamic metabolic profile of butyrate-induced HT29 cell differentiation 总被引:2,自引:0,他引:2
Boren J Lee WN Bassilian S Centelles JJ Lim S Ahmed S Boros LG Cascante M 《The Journal of biological chemistry》2003,278(31):28395-28402
Stable isotope-based dynamic metabolic profiling is applied in this paper to elucidate the mechanism by which butyrate induces cell differentiation in HT29 cells. We utilized butyrate-sensitive (HT29) cells incubated with [1,2-13C2]glucose or [1,2-13C2]butyrate as single tracers to observe the changes in metabolic fluxes in these cells. In HT29 cells, increasing concentrations of butyrate inhibited glucose uptake, glucose oxidation, and nucleic acid ribose synthesis in a dose-dependent fashion. Glucose carbon utilization for de novo fatty acid synthesis and tricarboxylic acid cycle flux was replaced by butyrate. We also demonstrated that these changes are not present in butyrate-resistant pancreatic adenocarcinoma MIA cells. The results suggest that the mechanism by which colon carcinoma cells acquire a differentiated phenotype is through a replacement of glucose for butyrate as the main carbon source for macromolecule biosynthesis and energy production. This provides a better understanding of cell differentiation through metabolic adaptive changes in response to butyrate in HT29 cells, demonstrating that variations in metabolic pathway substrate flow are powerful regulators of tumor cell proliferation and differentiation. 相似文献
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Comin-Anduix B Boros LG Marin S Boren J Callol-Massot C Centelles JJ Torres JL Agell N Bassilian S Cascante M 《The Journal of biological chemistry》2002,277(48):46408-46414
The fermented extract of wheat germ, trade name Avemar, is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of Avemar on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC(50) concentration of Avemar for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, Avemar inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G(1) peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodide- and annexin V-stained cells indicated that the growth-inhibiting effect of Avemar was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of Avemar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased (13)C incorporation and pentose cycle substrate flow into RNA ribose. This decrease in pentose cycle enzyme activities and carbon flow toward nucleic acid precursor synthesis provide the mechanistic understanding of the cell growth-controlling and apoptosis-inducing effects of fermented wheat germ. Avemar exhibits about a 50-fold higher IC(50) (10.02 mg/ml) for peripheral blood lymphocytes to induce a biological response, which provides the broad therapeutic window for this supplemental cancer treatment modality with no toxic effects. 相似文献
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Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and
insect hexamerins (storage proteins) are homologous gene products, although
the latter do not bind oxygen and do not possess the copper- binding
histidines present in the hemocyanins. An alignment of 19 amino acid
sequences of hemocyanin subunits and insect hexamerins was made, based on
the conservation of elements of secondary structure observed in X-ray
structures of two hemocyanin subunits. The alignment was analyzed using
parsimony and neighbor-joining methods. Results provide strong indications
for grouping together the sequences of the 2 crustacean hemocyanin
subunits, the 5 cheliceratan hemocyanin subunits, and the 12 insect
hexamerins. Within the insect clade, four methionine- rich proteins, four
arylphorins, and two juvenile hormone-suppressible proteins from
Lepidoptera, as well as two dipteran proteins, form four separate groups.
In the absence of an outgroup sequence, it is not possible to present
information about the ancestral state from which these proteins are
derived. Although this family of proteins clearly consists of homologous
gene products, there remain striking differences in gene organization and
site of biosynthesis of the proteins within the cell. Because studies on
18S and 12S rRNA sequences indicate a rather close relationship between
insects and crustaceans, we propose that hemocyanin is the ancestral
arthropod protein and that insect hexamerins lost their copper-binding
capability after divergence of the insects from the crustaceans.
相似文献
97.
Interactions of Photobleaching and Inorganic Nutrients in Determining Bacterial Growth on Colored Dissolved Organic Carbon 总被引:8,自引:0,他引:8
Abstract Bacteria are key organisms in the processing of dissolved organic carbon (DOC) in aquatic ecosystems. Their growth depends on both organic substrates and inorganic nutrients. The importance of allochthonous DOC, usually highly colored, as bacterial substrate can be modified by photobleaching. In this study, we examined how colored DOC (CDOC) photobleaching, and phosphorus (P) and nitrogen (N) availability, affect bacterial growth. Five experiments were conducted, manipulating nutrients (P and N) and sunlight exposure. In almost every case, nutrient additions had a significant, positive effect on bacterial abundance, production, and growth efficiency. Sunlight exposure (CDOC photobleaching) had a significant, positive effect on bacterial abundance and growth efficiency. We also found a significant, positive interaction between these two factors. Thus, bacterial use of CDOC was accelerated under sunlight exposure and enhanced P and N concentrations. In addition, the accumulation of cells in sunlight treatments was dependent on nutrient availability. More photobleached substrate was converted into bacterial cells in P- and N-enriched treatments. These results suggest nutrient availability may affect the biologically-mediated fate (new biomass vs respiration) of CDOC. 相似文献
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