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排序方式: 共有189条查询结果,搜索用时 31 毫秒
71.
Elonore Beurel Michel Kornprobst Marie-Jos Blivet-Van Eggelpoël Carmen Ruiz-Ruiz Axelle Cadoret Jacqueline Capeau Christle Desbois-Mouthon 《Experimental cell research》2004,300(2):488
Lithium exerts neuroprotective actions that involve the inhibition of glycogen synthase kinase-3β (GSK-3β). Otherwise, recent studies suggest that sustained GSK-3β inhibition is a hallmark of tumorigenesis. In this context, the present study was undertaken to examine whether lithium modulated cancer cell sensitivity to apoptosis induced by chemotherapy agents. We observed that, in different human cancer cell lines, lithium significantly reduced etoposide- and camptothecin-induced apoptosis. In HepG2 cells, lithium repressed drug induction of CD95 expression and clustering at the cell surface as well as caspase-8 activation. Lithium acted through deregulation of GSK-3β signaling since (1) it provoked a rapid and sustained phosphorylation of GSK-3β on the inhibitory serine 9 residue; (2) the GSK-3β inhibitor SB-415286 mimicked lithium effects by repressing drug-induced apoptosis and CD95 membrane expression; and (3) lithium promoted the disruption of nuclear GSK-3β/p53 complexes. Moreover, the overexpression of an inactivated GSK-3β mutant counteracted the stimulatory effects of etoposide and camptothecin on a luciferase reporter plasmid driven by a p53-responsive sequence from the CD95 gene. In conclusion, we provide the first evidence that lithium confers resistance to apoptosis in cancer cells through GSK-3β inhibition and subsequent repression of CD95 gene expression. Our study also highlights the concerted action of GSK-3β and p53 on CD95 gene expression. 相似文献
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Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size 总被引:24,自引:6,他引:18
The distributions of allele sizes at eight simple-sequence repeat (SSR) or
microsatellite loci in chimpanzees are found and compared with the
distributions previously obtained from several human populations. At
several loci, the differences in average allele size between chimpanzees
and humans are sufficiently small that there might be a constraint on the
evolution of average allele size. Furthermore, a model that allows for a
bias in the mutation process shows that for some loci a weak bias can
account for the observations. Several alleles at one of the loci (Mfd 59)
were sequenced. Differences between alleles of different lengths were found
to be more complex than previously assumed. An 8-base-pair deletion was
present in the nonvariable region of the chimpanzee locus. This locus
contains a previously unrecognized repeated region, which is imperfect in
humans and perfect in chimpanzees. The apparently greater opportunity for
mutation conferred by the two perfect repeat regions in chimpanzees is
reflected in the higher variance in repeat number at Mfd 59 in chimpanzees
than in humans. These data indicate that interspecific differences in
allele length are not always attributable to simple changes in the number
of repeats.
相似文献
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Fucosylated protein of retinal cone photoreceptor outer segments: morphological and biochemical analyses 下载免费PDF全文
Cone outer segments (OS) of the goldfish retina are diffusely labeled after intravitreal injection of [(3)H]fucose while rod OS remain unlabeled. By electron microscopic radioautography, the OS of red- and blue-sensitive cones are heavily labeled while green- sensitive cone OS are lightly labeled. The time-course and pattern of OS labeling in all cone types from 30 min to 24 h resemble that of incorporation of other sugars into rhodopsin in rod OS. The nature of the cone OS-specific fucosylated component(s) was examined using biochemical techniques. Cone OS were prelabeled by intravitreal injection of [(3)H]fucose 24 h before sacrifice. Photoreceptor OS were isolated using a discontinuous sucrose density gradient and it was verified by electron microscopic radioautography that the only source of radioactivity in the preparations was cone OS. The different cone types could be recognized by the heaviness of labeling, characteristic membrane spacing, and 'staining' of green cone OS in vitro with horseradish peroxidase. After acid hydrolysis of prelabeled photoreceptor membranes, 90 percent of the counts were in the neutral sugar fraction which was analyzed by thin-layer chromatography. Approximately 70 percent of the radioactivity co-chromatographed with authentic fucose. SDS-PAGE/fluorography of prelabeled photoreceptor membranes revealed a single radioactive component that was lightly stained with coomassie blue and showed an apparent molecular weight of 33,000. This cone-derived band was separated from unlabeled rod opsin which was well stained and showed an apparent mol wt of 38,000. Isoelectric focusing under denaturing conditions produced two major and one minor band of radioactivity with isoelectric points of 8.2, 8.6, and 8.8 respectively. No radioactivity was found in association with a stained band corresponding in isoelectric point to that of bovine opsin (pl, 6.2). The fucosylated component was readily digested by pronase, indicating its protein nature. Washing of the isolated OS with isotonic and hypotonic buffers failed to extract major amounts of the radioactivity, suggesting that the fucosylated component is an integral membrane protein. The presence of a fucosylated protein thus represents a major difference between cone and rod OS in the goldfish and has enabled us to identify cone OS in preparations of isolated photoreceptor membranes and to demonstrate the separation of a cone-derived glycoprotein from rod opsin. 相似文献
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78.
Structure and organization of the bovine beta-globin genes 总被引:1,自引:0,他引:1
Genomic clones spanning the entire cow beta-globin gene locus have been
isolated and characterized. These clones demonstrate that the linkage of
embryonic-like (epsilon) genes and pseudogenes (psi) to the previously
described fetal (gamma) and adult (beta) genes is as follows: 5'-epsilon
3-epsilon 4-psi 3-beta-epsilon 1-epsilon 2-psi 1- psi 2-gamma-3'. Present
data indicate that, like that of the goat, the fetal and adult genes arose
via block duplication of an ancestral four- gene set:
epsilon-epsilon-psi-beta. This duplication event preceded the divergence of
cows and goats, which occurred greater than or equal to 18-20 Myr ago.
However, cows do not have the additional four-gene block containing a
preadult/stress globin gene (beta C). Furthermore, the cow fetal cluster
contains an extra beta-like pseudogene, which apparently arose by a
small-scale duplication. The fixation of this duplication may indicate a
possible evolutionary role for pseudogenes.
相似文献
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