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11.
Hjerpe R Thomas Y Chen J Zemla A Curran S Shpiro N Dick LR Kurz T 《The Biochemical journal》2012,441(3):927-936
Ubiquitin and UBL (ubiquitin-like) modifiers are small proteins that covalently modify other proteins to alter their properties or behaviours. Ubiquitin modification (ubiquitylation) targets many substrates, often leading to their proteasomal degradation. NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) is the UBL most closely related to ubiquitin, and its best-studied role is the activation of CRLs (cullin-RING ubiquitin ligases) by its conjugation to a conserved C-terminal lysine residue on cullin proteins. The attachment of UBLs requires three UBL-specific enzymes, termed E1, E2 and E3, which are usually well insulated from parallel UBL pathways. In the present study, we report a new mode of NEDD8 conjugation (NEDDylation) whereby the UBL NEDD8 is linked to proteins by ubiquitin enzymes in vivo. We found that this atypical NEDDylation is independent of classical NEDD8 enzymes, conserved from yeast to mammals, and triggered by an increase in the NEDD8 to ubiquitin ratio. In cells, NEDD8 overexpression leads to this type of NEDDylation by increasing the concentration of NEDD8, whereas proteasome inhibition has the same effect by depleting free ubiquitin. We show that bortezomib, a proteasome inhibitor used in cancer therapy, triggers atypical NEDDylation in tissue culture, which suggests that a similar process may occur in patients receiving this treatment. 相似文献
12.
Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis
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Mandic A Viktorsson K Strandberg L Heiden T Hansson J Linder S Shoshan MC 《Molecular and cellular biology》2002,22(9):3003-3013
Calpain is a ubiquitous protease with potential involvement in apoptosis. We report that in human melanoma cells, cisplatin-induced calpain activation occurs early in apoptosis. Calpain activation and subsequent apoptosis were inhibited by calpeptin and PD150606, two calpain inhibitors with different modes of action. Furthermore, cisplatin induced cleavage of the BH3-only protein Bid, yielding a 14-kDa fragment similar to proapoptotic, caspase-cleaved Bid. However, Bid cleavage was inhibited by inhibitors of calpain, but not by inhibitors of caspases or of cathepsin L. Recombinant Bid was cleaved in vitro by both recombinant calpain and by lysates of cisplatin-treated cells. Cleavage was calpeptin sensitive, and the cleavage site was mapped between Gly70 and Arg71. Calpain-cleaved Bid induced cytochrome c release from isolated mitochondria. While calpeptin did not affect cisplatin-induced modulation of Bak to its proapoptotic conformation, a dominant-negative mutant of MEKK1 (dnMEKK) inhibited Bak modulation. dnMEKK did not, however, block Bid cleavage. The combination of dnMEKK and calpeptin had an additive inhibitory effect on apoptosis. In summary, calpain-mediated Bid cleavage is important in drug-induced apoptosis, and cisplatin induces at least two separate apoptotic signaling pathways resulting in Bid cleavage and Bak modulation, respectively. 相似文献
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Aleksandra Topic Marina Milenkovic Snezana Uskokovic-Markovic Dragana Vucicevic 《Biological trace element research》2010,134(3):296-306
Investigations of effective, orally active, and safe antidiabetic metallopharmaceuticals have been carried out during the
last two decades. It has been reported that tungsten compounds mimic the action of insulin in intact cell systems. As insulin
mimetics, the most investigated tungsten compound was sodium tungstate (ST), rarely investigated was tungstophosphoric acid
(WPA), but never alanine complex of tungstophosphoric acid (WPA-A). In this study, the insulin mimetic activity of three different
tungsten compounds, ST, WPA, and WPA-A, was evaluated by means of in vitro measurements of the glucose uptake and inhibition
of free fatty acids release from epinephrine-treated isolated rat white adipocytes. We investigated the influence of concentration
(lower and higher, 0.1 and 1.0 mM, respectively) and solvent: isotonic salt solution—saline (0.9% w/v of NaCl) and dimethyl sulfoxide (DMSO; 2% v/v), on the biological effect of tested compounds. Our experimental data showed that all of the three investigated tungsten
compounds possess insulin mimetic activity in vitro on the isolated adipocytes. Influence of concentration and solvents on
insulin mimetic effect for the certain tungsten compounds were: WPA was shown effect independently of concentration and solvents;
higher concentration and DMSO were significant decreasing insulin mimetic effect of ST; lower concentration and saline led
to decreasing effect of WPA-A. Generally, there were no differences in insulin mimetic effect of three tungsten compounds
in lower concentration and dissolved in DMSO. When saline was used as solvent, it was needed higher concentration of investigated
compounds to accomplish the same effect. In conclusion, our results suggest that low concentration (0.1 mM) of ST, WPA, and
WPA-A dissolved in 2% DMSO could be the good candidates for in vivo investigation of their antidiabetic properties. 相似文献
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Magorzata Walu-Miarka Aleksandra Trojak Przemysaw Miarka Maria Kapusta Ewa Kawalec Barbara Idzior-Walu Maciej T Maecki 《Innate immunity》2020,26(5):351
Elevated levels of plasma pentraxin 3 (PTX3), a marker of inflammation, are associated with the risk of developing cardiovascular diseases in the general population, as well as in patients with type 2 diabetes (DM2). In this study, we aimed to determine factors associated with PTX3 serum concentrations in men and women with DM2. The study included 116 consecutive patients (67 men and 49 women) with DM2 from an outpatient diabetic clinic. Men were characterised by lower age and higher uric acid, creatinine and bilirubin concentrations and waist/hip ratio than women. In women, low-density lipoprotein cholesterol (LDL-C) levels were higher than in men. In men, median (interquartile range) values of PTX3 concentration were 4.02 (1.99), and in women they were 4.53 (3.31) ng/ml (NS). In men, PTX3 concentrations correlated with total cholesterol (TC), triglycerides, apolipoprotein (Apo) C3, Apo B48, Glc and creatinine levels. In women, PTX3 correlated significantly with TC and LDL-C and Apo B100. Partial regression analysis revealed that after adjusting for age, PTX3 concentrations in men were significantly associated with TC, LDL-C, triglycerides, creatinine, Apo C3 and Apo B48, while in women they were associated with TC, LDL-C and Apo B100. The results could be of importance in sex-specific prevention of vascular complications in DM2 patients. 相似文献
18.
Mateusz Kurcinski Aleksandra Badaczewska‐Dawid Michal Kolinski Andrzej Kolinski Sebastian Kmiecik 《Protein science : a publication of the Protein Society》2020,29(1):211-222
Molecular docking of peptides to proteins can be a useful tool in the exploration of the possible peptide binding sites and poses. CABS‐dock is a method for protein–peptide docking that features significant conformational flexibility of both the peptide and the protein molecules during the peptide search for a binding site. The CABS‐dock has been made available as a web server and a standalone package. The web server is an easy to use tool with a simple web interface. The standalone package is a command‐line program dedicated to professional users. It offers a number of advanced features, analysis tools and support for large‐sized systems. In this article, we outline the current status of the CABS‐dock method, its recent developments, applications, and challenges ahead. 相似文献
19.
Anna Stepanova Maria Malunova Svetlana Salamaikina Renat Selimov Aleksandra Solov’eva 《Phyton》2021,90(2):543-552
Rhodiola quadrifida is a rare mountain medicinal plant whose root
extracts are used in traditional Chinese medicine as a hemostatic, antitussive,
and tonic in the treatment of gynecological diseases. The aim of the study was
to obtain R. quadrifida cultures at different degrees of differentiation in vitro
and compare their growth characteristics and the content of salidroside and rosavin. Hairy roots were obtained by incubating cotyledons and hypocotyls in a suspension of Agrobacterium rhizogenes strain A4. The presence of the rolB and
rolC genes was proven by polymerase chain reaction. The obtained roots were
cultivated in Murashige-Skoog medium (MS). Calluses were obtained from the
hairy roots in MS medium with the addition of hormones: 3 mg/L 2,4 D and
0.5 mg/L BAP. The presence of the main secondary metabolites of R. quadrifida,
salidroside and rosavin, in calluses and salidroside in hairy roots by HPLC/MS
was confirmed. The content of salidroside in callus culture was significantly
higher than in hairy roots, 0.158 and 0.047%, respectively. The content of rosavin
in callus culture was 0.07%. The content of rosavin and salidroside in callus culture
was close to the level of these substances in the rhizomes of R. quadrifida plants
growing in vivo, making this culture promising for its possible biotechnological use. 相似文献
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