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排序方式: 共有134条查询结果,搜索用时 542 毫秒
31.
Riad Schulz Thomas Emmrich Heidi Lemmerhirt Ulrike Leffler Kristin Sydow Carsten Hirt Thomas Kiefer Andreas Link Patrick J. Bednarski 《Bioorganic & medicinal chemistry letters》2012,22(21):6712-6715
Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ?fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly increased expression of the anti-oxidative enzyme glutathione peroxidase 1 (GPx1), GPx1 was investigated as a target for inhibitor development. Virtual screening of a library of diverse structures by docking them to the active site of the X-ray crystal structure of bovine GPx1 uncovered compounds that might block the enzyme. An enzyme assay confirmed an acylhydrazone heterocycle (3) with GPx inhibitory activity. Combinations of 3 with the anticancer drugs listed above led to reversal of resistance in the lymphoma cell lines. 相似文献
32.
33.
Reini W Bretveld Chris MG Thomas Paul TJ Scheepers Gerhard A Zielhuis Nel Roeleveld 《Reproductive biology and endocrinology : RB&E》2006,4(1):30
Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system
through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference
with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide
exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function
of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation:
1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition
and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms
are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation
of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies,
exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy,
spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal
function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity,
it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining
the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive
effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in
this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both
in toxicological and epidemiological settings. 相似文献
34.
35.
Doné SC Leibiger IB Efendiev R Katz AI Leibiger B Berggren PO Pedemonte CH Bertorello AM 《The Journal of biological chemistry》2002,277(19):17108-17111
In renal epithelial cells endocytosis of Na(+),K(+)-ATPase molecules is initiated by phosphorylation of its alpha(1)-subunit, leading to activation of phosphoinositide 3-kinase and adaptor protein-2 (AP-2)/clathrin recruitment. The present study was performed to establish the identity of the AP-2 recognition domain(s) within the Na(+),K(+)-ATPase alpha(1)-subunit. We identified a conserved sequence (Y(537)LEL) within the alpha(1)-subunit that represents an AP-2 binding site. Binding of AP-2 to the Na(+),K(+)-ATPase alpha(1)-subunit in response to dopamine (DA) was increased in OK cells stably expressing the wild type rodent alpha-subunit (OK-WT), but not in cells expressing the Y537A mutant (OK-Y537A). DA treatment was associated with increased alpha(1)-subunit abundance in clathrin vesicles from OK-WT but not from OK-Y537A cells. In addition, this mutation also impaired the ability of DA to inhibit Na(+),K(+)-ATPase activity. Because phorbol esters increase Na(+),K(+)-ATPase activity in OK cells, and this effect was not affected by the Y537A mutation, the present results suggest that the identified motif is specifically required for DA-induced AP-2 binding and Na(+),K(+)-ATPase endocytosis. 相似文献
36.
Phylogeny of the Drosophila saltans species group based on combined analysis of nuclear and mitochondrial DNA sequences 总被引:2,自引:0,他引:2
Nucleotide sequences from two nuclear loci, alcohol dehydrogenase and
internal transcribed spacer-1 of the nuclear ribosomal DNA repeats, and two
mitochondrial genes, cytochrome oxidase I and cytochrome oxidase II, were
determined from nine species in the Drosophila saltans species group. The
partition homogeneity test and partitioned Bremer support were used to
measure incongruence between phylogenetic hypotheses generated from
individual partitions. Individual loci were generally congruent with each
other and consistent with the previously proposed morphological hypothesis,
although they differed in level of resolution. Since extreme conflict
between partitions did not exist, the data were combined and analyzed
simultaneously. The total evidence method gave a more resolved and highly
supported phylogeny, as indicated by bootstrap proportions and decay
indices, than did any of the individual analyses. The cordata and elliptica
subgroups, considered to have diverged early in the history of the D.
saltans group, were sister taxa to the remainder of the saltans group. The
sturtevanti subgroup, represented by D. milleri and D. sturtevanti,
occupies an intermediate position in this phylogeny. The saltans and
parasaltans subgroups are sister clades and occupy the most recently
derived portion of the phylogeny. As with previous morphological studies,
phylogenetic relationships within the saltans subgroup were not
satisfactorily resolved by the molecular data.
相似文献
37.
Nucleotide sequence comparisons were used to investigate the evolution of P
transposable elements and the possibility that horizontal transfer has
played a role in their occurrence in natural populations of Drosophila and
other Diptera. The phylogeny of P elements was examined using published
sequences from eight dipteran taxa and a new, partial sequence from
Scaptomyza elmoi. The results from a number of different analyses are
highly consistent and reveal a P-element phylogeny that contradicts the
phylogeny of the species. At least three instances of horizontal transfer
are necessary to explain this incongruence, but other explanations cannot
be ruled out at this time.
相似文献
38.
Measurements of serotonin (5-HT), dopamine (DA), and noradrenaline, and of 5-HT and DA metabolites, were obtained by HPLC from 16 brain regions and the spinal cord of 5-HT(1A) or 5-HT(1B) knockout and wild-type mice of the 129/Sv strain. In 5-HT(1A) knockouts, 5-HT concentrations were unchanged throughout, but levels of 5-HT metabolites were higher than those of the wild type in dorsal/medial raphe nuclei, olfactory bulb, substantia nigra, and locus coeruleus. This was taken as an indication of increased 5-HT turnover, reflecting an augmented basal activity of midbrain raphe neurons and consequent increase in their somatodendritic and axon terminal release of 5-HT. It provided a likely explanation for the increased anxious-like behavior observed in 5-HT(1A) knockout mice. Concomitant increases in DA content and/or DA turnover were interpreted as the result of a disinhibition of DA, whereas increases in noradrenaline concentration in some territories of projection of the locus coeruleus could reflect a diminished activity of its neurons. In 5-HT(1B) knockouts, 5-HT concentrations were lower than those of the wild type in nucleus accumbens, locus coeruleus, spinal cord, and probably also several other territories of 5-HT innervation. A decrease in DA, associated with increased DA turnover, was measured in nucleus accumbens. These changes in 5-HT and DA metabolism were consistent with the increased aggressiveness and the supersensitivity to cocaine reported in 5-HT(1B) knockout mice. Thus, markedly different alterations in CNS monoamine metabolism may contribute to the opposite behavioral phenotypes of these two knockouts. 相似文献
39.
Differences in growth and water relations among Phaseolus vulgaris cultivars in response to induced drought stress 总被引:3,自引:0,他引:3
Costa França MG Pham Thi AT Pimentel C Pereyra Rossiello RO Zuily-Fodil Y Laffray D 《Environmental and Experimental Botany》2000,43(3):227-237
Relatively little ecophysiological research has been conducted to determine the responses to drought of Phaseolus vulgaris. Four bean cultivars (cvs.) from Brazil, A320, Carioca, Ouro Negro and Xodó were submitted to an imposed water deficit in order to evaluate the importance of some adaptive mechanisms of drought resistance through the analysis of growth parameters, water status, gas exchange and indicators of tolerance mechanisms at the cellular level. During the drought treatment, relative growth rates were more reduced for A320 and Xodó than Carioca and Ouro Negro. A320 closed its stomata very rapidly and complete stomatal closure was obtained at Psi(w)=-0.6 MPa, in contrast to the other cvs. where stomata were fully closed only at Psi(w)=-0.9 MPa. Net assimilation rates were closely related to stomatal conductances. Mechanisms at the cellular level appeared to be mostly important for higher tolerance. Carioca and Ouro Negro, when compared to A320 and Xodó, were characterized by having better drought tolerance mechanisms and higher tissue water retention capacity leading to a better growth under water deficits. The leaf dehydration rates of those cvs. were slow whereas those of the drought sensitive cvs. were rapid. The results were confirmed by the electrolyte leakage test and leaf osmotic potential measurements, which indicated higher membrane resistance and osmotic adjustment in the two tolerant cvs. Carioca and Ouro Negro. It appears from this study that despite being cultivated in the same geographical region, the four cvs. of P. vulgaris displayed somewhat different drought adaptive capacities for prolonged drought during the vegetative phase. 相似文献
40.
Boyer L Elias R Taoubi K Debrauwer L Faure R Baghdikian B Balansard G 《Phytochemical analysis : PCA》2005,16(5):375-379
Five lignans, phillyrin (1), pinoresinol-beta-D-glucoside (2), pinoresinol di-beta-D-glucoside (3), phillyrin-2-O-beta-D-glucoside (6), phillyrin-6-O-beta-D-glucoside (7), and three secoiridoids, oleuropein (4), ligustroside (5) and angustifolioside B (8), have been isolated from the root bark of Chionanthus virginicus L. (Oleaceae), a raw material used in the commercial preparation of homeopathy tinctures. Compound 6 is a new lignan, and compounds 2, 3, 4, 5, 7 and 8 are described for the first time in the title plant. The structures of these compounds were elucidated by spectroscopic methods (NMR and HPLC-MS). An isocratic HPLC method for the rapid characterisation and quantification of the major constituents, 1 and 4, of the root bark is described and validated. 相似文献