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11.
Reactive oxygen and nitrogen species produced by metabolism and immune defenses can cause extensive damage to biomolecules. To counteract this damage, organisms rely on exogenous and endogenous antioxidants, although their relative importance in maintaining redox balance is unclear. We supplemented captive greenfinches with dietary antioxidants--carotenoids and vitamin E--and injected them with an inflammatory agent, phytohemagglutinin. Compared to controls, immune-challenged birds circulated more lipid peroxidation products but also increased total plasma antioxidativity. Carotenoid (but not vitamin E) supplementation generally reduced lipid peroxidation, but this did not compensate for the effects of immune activation. Levels of an endogenous antioxidant--uric acid--strongly contributed to plasma antioxidativity. We found no evidence that dietary antioxidants are immunostimulatory. These results demonstrate the antioxidant function of carotenoids in birds and show that simultaneous assessment of oxidative stress-driven damage, antioxidant barrier, and individual antioxidants is critical for explaining the potential costs of immune system activation. 相似文献
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The epilimnetic phytoplankton and its relations to nutrient content in Lake Verevi through the whole vegetation period in 2000 were studied. Lake Verevi (surface 12.6 ha, mean depth 3.6 m, maximum depth 11 m) is a hypertrophic hard-water lake, where the so-called spring meromixis occurs due to an extremely warm spring. Most dissolved nutrients in the epilimnion were low already in spring, and their concentrations were quite stable during the study period. The concentration of total silicon was very low in spring but increased rapidly in summer. Total phosphorus followed the pattern for stratified eutrophic lakes, and total nitrogen was quite high. The stoichiometric N:P ratio fluctuated between 25 and 81. The dynamics of phytoplankton biomass with a spring peak from April to May and a late summer peak from July to August is typical of Estonian eutrophic lakes. Green algae and chrysophytes occurred in the phytoplankton throughout the vegetation period. The spring peak was dominated by diatoms (Synedra ulna and Synedra acus var. angustissima) and the summer peak was caused by Aphanizomenon klebahnii and Ceratium hirundinella. The study showed that in physically stratified systems, the total concentration of limiting resources and plain physical factors (light and temperature) may be more important in the determination of phytoplankton dominants than different resource ratios. A combination of light and temperature optimum, along with nutrient utilization and transport capacity, effectively segregates phytoplankton species and can be used for the explanation of seasonal succession pattern. 相似文献
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Oselin K Anier K Tamm R Kallassalu K Mäeorg U 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,834(1-2):77-83
Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) is the key enzyme in the metabolism of thiopurine drugs. Determination of TPMT activity has been used for the individualization of thiopurine dose. We developed HPLC-UV assay for the determination of TPMT activity in human erythrocytes using 6-mercaptopurine as a substrate. Various extraction and chromatographic conditions were compared. In-house developed extraction with acetonitrile provided the lowest limit of quantification. TPMT activity was determined in 99 previously genotyped healthy Estonians. TPMT activity was expressed as the formation of 6-methylmercaptopurine ng/ml/h and normalized either to haemoglobin, haematocrit, erythrocyte count or protein content. The receiver-operating characteristic curve analysis revealed similar accuracy values for TPMT activity in predicting heterozygous and wild type individuals for each method of calculation. In healthy Estonians, TPMT activity varied from 21.5 to 129.6 ng/ml/h. For heterozygous individuals (n = 18), TPMT activity was 48.1 +/- 11.7 ng/ml/h. Wild type individuals (n = 81) revealed significantly higher TPMT activity 79.3 +/- 20.7 ng/ml/h (P < 0.001). This sensitive HPLC assay for quantitative determination of TPMT activity could easily be used in clinical settings. Under constant experimental conditions for haemolysate preparation no normalization is required. 相似文献
14.
T Kaambre V Chekulayev I Shevchuk M Karu-Varikmaa N Timohhina K Tepp J Bogovskaja R Kütner V Valvere V Saks 《Journal of bioenergetics and biomembranes》2012,44(5):539-558
The aim of this study was to analyze quantitatively cellular respiration in intraoperational tissue samples taken from human breast cancer (BC) patients. We used oxygraphy and the permeabilized cell techniques in combination with Metabolic Control Analysis (MCA) to measure a corresponding flux control coefficient (FCC). The activity of all components of ATP synthasome, and respiratory chain complexes was found to be significantly increased in human BC cells in situ as compared to the adjacent control tissue. FCC(s) were determined upon direct activation of respiration with exogenously-added ADP and by titrating the complexes with their specific inhibitors to stepwise decrease their activity. MCA showed very high sensitivity of all complexes and carriers studied in human BC cells to inhibition as compared to mitochondria in normal oxidative tissues. The sum of FCC(s) for all ATP synthasome and respiratory chain components was found to be around 4, and the value exceeded significantly that for normal tissue (close to 1). In BC cells, the key sites of the regulation of respiration are Complex IV (FCC?=?0.74), ATP synthase (FCC?=?0.61), and phosphate carrier (FCC?=?0.60); these FCC(s) exceed considerably (~10-fold) those for normal oxidative tissues. In human BC cells, the outer mitochondrial membrane is characterized by an increased permeability towards adenine nucleotides, the mean value of the apparent K(m) for ADP being equal to 114.8?±?13.6?μM. Our data support the two-compartment hypothesis of tumor metabolism, the high sum of FCC(s) showing structural and functional organization of mitochondrial respiratory chain and ATP synthasome as supercomplexes in human BC. 相似文献
15.
Inge W. Nilsen Kersti
verb Ragnar L. Olsen 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2001,129(4)
Sequence analysis of short fragments resulting from trypsin digestion of the thermolabile shrimp alkaline phosphatase (SAP) from Northern shrimp Pandalus borealis formed the basis for amplification of its encoding cDNA. The predicted protein sequence was recognized as containing the consensus alkaline phosphatase motif comprising the active site of this protein family. Protein sequence homology searches identified several eukaryote alkaline phosphatases with which the 475-amino acid SAP polypeptide revealed shares 45% amino acid sequence identity. Residues for potential metal binding seem to be conserved in these proteins. The predicted 54-kDa molecular mass of SAP is smaller than previously reported, but is consistent with our recent SDS-PAGE analysis of the native protein. Compared to its homologs, the shrimp enzyme has a surplus of negatively charged amino acids, while the relative number of prolines is lower and the frequency of aromatic residues is higher than in mesophilic counterparts. 相似文献
16.
Julia Mantaj Paul J. M. Jackson Kersti Karu Khondaker M. Rahman David E. Thurston 《PloS one》2016,11(4)
Pyrrolobenzodiazepines (PBDs) are covalent-binding DNA-interactive agents with growing importance as payloads in Antibody Drug Conjugates (ADCs). Until now, PBDs were thought to covalently bond to C2-NH2 groups of guanines in the DNA-minor groove across a three-base-pair recognition sequence. Using HPLC/MS methodology with designed hairpin and duplex oligonucleotides, we have now demonstrated that the PBD Dimer SJG-136 and the C8-conjugated PBD Monomer GWL-78 can covalently bond to a terminal guanine of DNA, with the PBD skeleton spanning only two base pairs. Control experiments with the non-C8-conjugated anthramycin along with molecular dynamics simulations suggest that the C8-substituent of a PBD Monomer, or one-half of a PBD Dimer, may provide stability for the adduct. This observation highlights the importance of PBD C8-substituents, and also suggests that PBDs may bind to terminal guanines within stretches of DNA in cells, thus representing a potentially novel mechanism of action at the end of DNA strand breaks. 相似文献
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18.
It is well known that the positively charged polyamines have a DNA-stabilizing function and that polyamine depletion alters chromatin function. We have previously shown that polyamine depletion causes an S phase prolongation, and others have shown that there is an accumulation of Okazaki-like fragments in polyamine-depleted cells. In the present study, we have used the comet assay to investigate polyamine depletion-induced DNA strand breaks. Three breast cancer cell lines and one normal-like breast cell line were treated with the polyamine analogue N(1),N(11)-diethylnorspermine or with the polyamine biosynthesis inhibitor 4-amidinoindan-1-one 2'-amidinohydrazone (CGP 48664). The comet assay showed that polyamine depletion resulted in DNA strand breaks. We also show that these DNA strand breaks occurred in cells where there was no expression of gamma-H2AX, which is a marker of DNA double-strand breaks. Thus, our conclusion is that polyamine depletion causes DNA single-strand breaks, which may be the cause for the observed delay in S phase progression. 相似文献
19.
Chen J Han M Manisastry SM Trotta P Serrano MC Huhta JC Linask KK 《Birth defects research. Part A, Clinical and molecular teratology》2008,82(7):508-518
BACKGROUND: Lithium (Li) has been associated with cardiac teratogenicity in the developing fetus. We took advantage of the association of therapeutic administration of Li with an increase in heart defects to gain insight into both normal and pathological heart and valve development with GSK‐3 inhibition. The objective of this study was to define whether Li mimicry of canonical Wnt/β‐catenin signaling induces cardiac valve defects. METHODS: Li was administered by a single intraperitoneal injection to the pregnant mouse on embryonic day E6.75, much earlier than heretofore analyzed. On E15.5 developing heart defects were defined by Doppler ultrasound. The embryonic hearts were analyzed for changes in patterning of active canonical Wnt expression and nuclear factor of the activated T cells‐c1 (NFATc1), both key regulators of valve development. Li‐exposed chick embryos were used to define the early cell populations during gastrulation that are susceptible to GSK‐3 inhibition and may relate to valve formation. RESULTS: Li exposure during gastrulation decreased the number of prechordal plate (PP) cells that reached the anterior intestinal portal, a region associated with valve development. Li decreased expression of Hex, an endoderm cardiac inducing molecule, normally also expressed by the PP cells, and of Sox 4 at the anterior intestinal portal and NFAT, critical factors in valvulogenesis. CONCLUSIONS: Cells existing already during gastrulation are associated with valve formation days later. The Wnt/β‐catenin signaling in PP cells is normally repressed by Wnt antagonists and Hex is up‐regulated. The antagonism occurring at the receptor level is bypassed by Li exposure by its intracellular inactivation of GSK‐3 directly to augment Wnt signaling. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc. 相似文献
20.
Janardan P. Pandey Paul J. Nietert Kersti Klaamas Oleg Kurtenkov 《Cancer immunology, immunotherapy : CII》2009,58(12):2025-2029
High levels of antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in adenocarcinomas, are associated
with good prognosis in patients with breast cancer. The aim of the present investigation was to determine whether GM and KM
allotypes—genetic markers of IgG heavy chains and κ-type light chains, respectively—contribute to the magnitude of natural
antibody responsiveness to MUC1 in patients with breast cancer. A total of 153 Caucasian subjects with breast cancer were
allotyped for several GM and KM markers. These subjects were also characterized for IgG and IgM antibodies to MUC1. Anti-MUC1
IgG antibody levels in subjects who were carriers of the immunoglobulin γ2 allele GM 23 were significantly higher than in
those who were noncarriers (P = 0.003). These results could potentially divide the population into high or low responders to MUC1, which has important
implications for MUC1-based immunotherapeutic interventions in breast cancer. 相似文献