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91.
Mustafa Ark Aysun Özdemir Belgin Polat 《Apoptosis : an international journal on programmed cell death》2010,15(12):1494-1506
Ouabain, a specific Na+/K+-ATPase inhibitor, has recently been identified as a mammalian hormone. Its elevated concentrations in human plasma have also
been associated with pathogenesis of several diseases. Recent studies have shown that ouabain induces aponecrotic cell death
in a cell-type- and dose-dependent manner. However, the exact mechanism of ouabain-induced cell death is not fully understood.
The Rho GTPase effectors Rho kinases-1 and -2 (Rock-1 and Rock-2) which play central roles in the organization of the actin
cytoskeleton, involve in several models of apoptosis. In this study, we investigated the possible involvement of Rocks in
ouabain-induced human umbilical vein endothelial cell (HUVEC) apoptosis. Ouabain treatment resulted in loss of cell–cell and
cell–substratum adhesion and apoptotic blebbing. Pretreatment of cells with Y-27632, a specific Rock inhibitor, resulted in
the inhibition of cell-to-cell detachment and formation of membrane blebs. However, Y-27632 did not prevent ouabain-induced
cell–substratum detachment. Instead, treatment with Y-27632 actually accelerated this process. Ouabain treatment induced cleavage
of Rock-1 and Rock-2, which was prevented by caspase-3 and caspase-2 specific inhibitors z-DEVD-fmk and z-VDVAD-fmk, respectively.
Ouabain-induced Rock-2 cleavage generated a fragment of approximately 140 kDa corresponding to the consensus sequence of caspase-2
on the carboxy terminus of Rock-2. Although it has been previously shown that Rock-2 was cleaved by caspase-2, we have identified
here a novel cleavage site and fragment of Rock-2. Our data indicate that ouabain induces both Rock-1 and Rock-2 cleavage
via caspase-dependent mechanisms and provide evidence that Rocks are involved in ouabain-induced cell-to-cell detachment and
apoptosis. 相似文献
92.
Background
Large-scale compilation of gene expression microarray datasets across diverse biological phenotypes provided a means of gathering a priori knowledge in the form of identification and annotation of bimodal genes in the human and mouse genomes. These switch-like genes consist of 15% of known human genes, and are enriched with genes coding for extracellular and membrane proteins. It is of interest to determine the prediction potential of bimodal genes for class discovery in large-scale datasets. 相似文献93.
94.
Plasma and inflammatory fluid kininogen levels, and blood and inflammatory fluid free kinin levels were determined in rats 24 h after the injection of carrageenin into an air pouch. Plasma T-kininogen levels increased 7-fold. In the inflammatory fluid levels reached 8 μg/ml. Blood levels of free kinin showed a 5-fold increase. The kinins were identified on HPLC as T-kinin (Ile-Ser-bradykinin) and bradykinin, 63 and 37%, respectively. These results indicate for the first time that free T-kinin as well as bradykinin is released during an inflammatory response in rat and confirms our previous finding that T-kininogen may be a major acutephase protein in inflammation.
T-kinin T-kininogen Bradykinin Inflammation Acute-phase protein Carrageenin 相似文献
95.
Trichotoxin A40. Purification by counter-current distribution and sequencing of isolated fragments 总被引:2,自引:0,他引:2
The isolation of the membrane-modifying polypeptide antibiotics from the mycelium of Trichoderma viride 5242 was optimized via extraction with dichloromethane and chromatography on Sephadex LH-20. The components trichotoxin A40 and A50 were separated from each other and purified by multiplicative counter-current distribution. The sequence of proteinase-resistant trichotoxin A40 was determined by combined gas chromatography and mass spectrometry of three isolated N-acetylated dodecapeptides and two N-prolylhexapeptides obtained after selective trifluoroacetolysis. Including amino acid exchanges due to natural microheterogeneity, the sequence is Ac-Aib-Gly(LAla)-Aib-LLeu-Aib-LGln-Aib-Aib-Aib(LAla )-LAla-Aib-Aib-LPro-LLeu -Aib-DIva(Aib)-LGlu-LValol. In contrast to the eicosapeptide alamethicin, trichotoxin A40 contains only 18 residues, with a higher proportion of alpha-aminoisobutyric acid (Aib), C-terminal L-valinol (Vol), one D-isovaline (Iva) and no proline at the N-terminal part. 相似文献
96.
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98.
Chemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance. 相似文献
99.
Selenium (Se), zinc (Zn), copper (Cu), and antioxidant enzyme (superoxide dismutase [SOD] and glutathione peroxidase [GSH-Px]) levels in sera were detected in Behçet patients. Age and sex matched controls were used to find out if oxidative stress takes place in the etiopathogenesis of Behçet’s disease. Superoxide dismutase levels were found to be lower in the whole patients group when compared to controls. In whole patients and inactive patients’ group Zn and Se levels were found to be higher, but not different in the active patients group when compared to controls. No significant difference was found between the groups as Cu and glutathione peroxidase levels were taken into consideration. According to the results of the present study, SOD level is low in Behçet’s disease patients’ sera independent from the phase of the disease, and as a result of decreased SOD activity, increased production of free oxygen radicals may play a role in the etiopathogenesis of the disease. 相似文献
100.
Regulation of FAS ligand expression by chemokine ligand 2 in human endometrial cells 总被引:3,自引:0,他引:3
Human endometrium is a dynamic tissue under the influence of numerous hormones, growth factors, and cytokines interacting to maintain a balance of cellular growth, differentiation, and apoptosis. We have previously demonstrated that several factors including interleukin-8, extracellular matrix, and steroid hormones modulate FASLG, one of the apoptotic molecules, in human endometrium. Chemokine ligand 2 (CCL2), a monocyte chemoattractant and activating factor, is a cytokine involved in endometrial function. CCL2 is elevated in the peritoneal fluid of women with endometriosis. We hypothesize that increased levels of CCL2 in the endometriotic environment may upregulate FASLG expression in human endometrial stromal cells and induce a local immunotolerance in endometriosis. To test our hypothesis, we studied the in vitro regulation of FASLG expression and apoptosis by CCL2 in endometrial stromal cells. Western blot analysis revealed that CCL2 upregulated FASLG protein expression in cultured endometrial stromal cells. Based on semiquantitative RT-PCR analysis, CCL2 did not alter either FAS or FASLG mRNA expression in endometrial stromal cells. Immunocytochemistry results from the same cells treated with CCL2 demonstrated upregulation of FASLG protein expression. CCL2 did not change rate of apoptosis in endometrial stromal cells as evaluated by TUNEL assay. However, an increased apoptotic rate was detected in Jurkat (T lymphocytes) cells cocultured with endometrial stromal cells previously treated with CCL2. We speculate that increased FASLG expression by CCL2 may induce apoptosis of T lymphocytes and thus produce an immunotolerant environment for the development of ectopic implants. 相似文献