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181.
目的:研究表没食子儿茶素没食子酸酯(Epigallaocatechin-3-gallate,EGCG)时人结肠癌HT-29细胞增殖的影响.方法:实验分为EGCG不同浓度处理组和阴性对照组.采用MTT比色法检测EGCG(30μg/mL、40μg/mL、50μg/mL、60μg/mL、70μg/mL)对HT-29细胞的生长影响;应用流式细胞术分析EGCG对HT-29细胞周期分布的影响;免疫印迹观测EGCG对HT-29细胞p38MAPK、cyclinD1蛋白表达的影响.结果:MTT比色结果显示.不同浓度EGCG(30μg/ml、40μg/ml、50μg/ml、60μg/ml)对HT-29细胞具有明显的生长抑制作用,并呈剂量-效应依赖关系(P<0.05);流式细胞术分析显示,EGCG诱导人结肠癌细胞G1期阻滞,且随着处理时间的延长,其诱导周期阻滞的效应越明显(P<0.05);蛋白免疫印迹显示.总的p38MAPK不随处理时间和浓度的改变而改变,但是磷酸化的p38MAPK蛋白的表达随处理时间和处理浓度的增加而明显增加,而CyclinD1蛋白的表达随处理浓度的增加而明显减少.结论:EGCG诱导HT-29细胞G1期阻滞,抑制细胞增殖,可能与活化p38MAPK,下调CyclinD1蛋白表达有关. 相似文献
182.
Schiavon E Sacco T Cassulini RR Gurrola G Tempia F Possani LD Wanke E 《The Journal of biological chemistry》2006,281(29):20326-20337
Resurgent currents are functionally crucial in sustaining the high frequency firing of cerebellar Purkinje neurons expressing Na(v)1.6 channels. Beta-scorpion toxins, such as CssIV, induce a left shift in the voltage-dependent activation of Na(v)1.2 channels by "trapping" the IIS4 voltage sensor segment. We found that the dangerous Cn2 beta-scorpion peptide induces both the left shift voltage-dependent activation and a transient resurgent current only in human Na(v)1.6 channels (among 1.1-1.7), whereas CssIV did not induce the resurgent current. Cn2 also produced both actions in mouse Purkinje cells. These findings suggest that only distinct beta-toxins produce resurgent currents. We suggest that the novel and unique selectivity of Cn2 could make it a model drug to replace deep brain stimulation of the subthalamic nucleus in patients with Parkinson disease. 相似文献
183.
Molecular evolution of olfactomedin 总被引:2,自引:0,他引:2
Olfactomedin is a secreted polymeric glycoprotein of unknown function,
originally discovered at the mucociliary surface of the amphibian olfactory
neuroepithelium and subsequently found throughout the mammalian brain. As a
first step toward elucidating the function of olfactomedin, its
phylogenetic history was examined to identify conserved structural motifs.
Such conserved motifs may have functional significance and provide targets
for future mutagenesis studies aimed at establishing the function of this
protein. Previous studies revealed 33% amino acid sequence identity between
rat and frog olfactomedins in their carboxyl terminal segments. Further
analysis, however, reveals more extensive homologies throughout the
molecule. Despite significant sequence divergence, cysteines essential for
homopolymer formation such as the CXC motif near the amino terminus are
conserved, as is the characteristic glycosylation pattern, suggesting that
these posttranslational modifications are essential for function.
Furthermore, evolutionary analysis of a region of 53 amino acids of fish,
frog, rat, mouse, and human olfactomedins indicates that an ancestral
olfactomedin gene arose before the evolution of terrestrial vertebrates and
evolved independently in teleost, amphibian, and mammalian lineages.
Indeed, a distant olfactomedin homolog was identified in Caenorhabditis
elegans. Although the amino acid sequence of this invertebrate protein is
longer and highly divergent compared with its vertebrate homologs, the
protein from C. elegans shows remarkable similarities in terms of conserved
motifs and posttranslational modification sites. Six universally conserved
motifs were identified, and five of these are clustered in the carboxyl
terminal half of the protein. Sequence comparisons indicate that evolution
of the N-terminal half of the molecule involved extensive insertions and
deletions; the C-terminal segment evolved mostly through point mutations,
at least during vertebrate evolution. The widespread occurrence of
olfactomedin among vertebrates and invertebrates underscores the notion
that this protein has a function of universal importance. Furthermore,
extensive modification of its N-terminal half and the acquisition of a
C-terminal SDEL endoplasmic-reticulum- targeting sequence may have enabled
olfactomedin to adopt new functions in the mammalian central nervous
system.
相似文献
184.
M Baldo M Schiavon P A Cicogna P Boccato F Mazzoleni 《Plastic and reconstructive surgery》1992,90(6):1073-1076
A case is presented of a 44-year-old Caucasian man who was operated on in October of 1988 for a cutaneous melanoma in his trunk and who in the space of 1 year manifested a single subcutaneous nodule compatible with a metastasis of melanoma by fine-needle aspiration biopsy. No other abnormal findings were revealed by physical and instrumental examinations. During the subsequent hospitalization, we witnessed (in conjunction with the occurrence of painful symptoms in the hands of an inflammatory nature) the total, progressive, spontaneous regression of the metastasis, which was confirmed by the clinic and the tests. After 15 months of follow-up, the patient has not shown any further signs of illness. 相似文献
185.
A comparative pharmacokinetic and biodistribution investigation of polymer-protein conjugates prepared with various amphiphilic polymers was carried out using uricase as a model. Four polymer-uricase derivatives have been obtained by covalent binding of a similar number of polymer chains of (a) linear poly(ethylene glycol) (Mw 5000 Da); (b) branched poly(ethylene glycol) (Mw 10 000 Da); (c) poly(N-vinylpyrrolidone) (Mw 6000 Da); (d) poly(N-acryloilmorpholine) (Mw 6000 Da). By intravenous administration to Balb/c mice, the conjugates displayed different pharmacokinetic and organ distribution behaviors. (1) The unmodified enzyme and the poly(N-vinylpyrrolidone) conjugate were the enzyme forms with the shortest and the longest permanence in blood respectively (mean residence time 45 and 4378 min). (2) Native uricase was found to localize soon after administration significantly in heart, lungs, and liver from where it was also rapidly cleared. (3) The poly(N-acryloilmorpholine) derivative showed the highest concentration levels in liver (up to 25.5% of the dose) and considerable accumulation took also place in the other considered organs. (4) Poly(N-vinylpyrrolidone)-uricase displayed a relevant tropism for liver but low uptake indexes were found for the other organs. (5) The branched poly(ethylene glycol) derivative accumulated preferentially in liver and spleen. (6) The linear poly(ethylene glycol) conjugate was, among the various uricase forms, the species with the lowest distribution levels in all the examined organs. (7) Finally, all the enzyme forms slowly disposed in kidneys with higher levels for the poly(N-acryloilmorpholine) derivative (15% after 2880 min) and unmodified uricase (14% after 1440 min). 相似文献
186.
F M Veronese O Schiavon E Boccù C A Benassi A Fontana 《International journal of peptide and protein research》1984,24(6):557-562
The octameric enolase from Bacillus stearothermophilus was immobilized onto Sepharose 4B activated by the cyanogen bromide reaction under conditions for achieving essentially a single-point attachment. The immobilized enzyme was dissociated with guanidine hydrochloride to yield bound monomeric enolase. The Sepharose-bound subunit regained activity upon removal of the denaturant. It was also possible to rehydribize immobilized monomers to native octamers. Of note, the thermal stability of the immobilized enolase subunit does not appreciably differ from that of the parent soluble octameric enzyme. Thus, these results indicate that single subunits of thermophilic enolase are active and that oligomerization is not a prerequisite for the enzymic activity as well as for thermal stability. 相似文献
187.
The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus 总被引:1,自引:0,他引:1
Padgett RW; Loeb DD; Snyder LR; Edgell MH; Hutchison CA d 《Molecular biology and evolution》1987,4(1):30-45
Recombinant DNA clones have been isolated that contain 80 kb of the
beta-globin complex from the deer mouse, Peromyscus maniculatus.
Comparisons of this complex with that from the laboratory mouse, Mus
domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3,
Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin
complex since the two species diverged. Unlike other mammals studied thus
far, the deer mouse possesses three adult genes. Partial sequence analysis
indicates that each of the three adult genes is intact and hence may be
functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to
genomic blots from Peromyscus reveals that it has a homologous counterpart
in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO
and Hbb-bhl, are also found in Peromyscus. The strong hybridization between
the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO
genes suggest that both pairs are important for the ontogeny of these mice
although no known product has been identified for the Hbb-bhO genes. The
presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication
that created this related gene set occurred before the two lineages
diverged. A single gene for Hbb-y has been isolated from Peromyscus. The
adult region in Peromyscus has undergone significant divergence from the
same region in Mus, having three rather than two adult genes, the
acquisition of at least 15 kb of extra DNA relative to Mus, and possibly
the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in
contrast, contains the same set of genes apparently distributed over the
same amount of DNA as in the Mus beta- globin complex. This observation
suggests that the embryonic region of the complex is more evolutionarily
stable than the adult region.
相似文献