排序方式: 共有73条查询结果,搜索用时 312 毫秒
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Liu J Plotnikov A Banerjee A Suresh Kumar KG Ragimbeau J Marijanovic Z Baker DP Pellegrini S Fuchs SY 《Biochemical and biophysical research communications》2008,367(2):388-393
Ligand-specific negative regulation of cytokine-induced signaling relies on down regulation of the cytokine receptors. Down regulation of the IFNAR1 sub-unit of the Type I interferon (IFN) receptor proceeds via lysosomal receptor proteolysis, which is triggered by ubiquitination that depends on IFNAR1 serine phosphorylation. While IFN-inducible phosphorylation, ubiquitination, and degradation requires the catalytic activity of the Tyk2 Janus kinase, here we found the ligand- and Tyk2-independent pathway that promotes IFNAR1 phosphorylation, ubiquitination, and degradation when IFNAR1 is expressed at high levels. A major cellular kinase activity that is responsible for IFNAR1 phosphorylation in vitro does not depend on either ligand or Tyk2 activity. Inhibition of ligand-independent IFNAR1 degradation suppresses cell proliferation. We discuss the signaling events that might lead to ubiquitination and degradation of IFNAR1 via ligand-dependent and independent pathways and their potential physiologic significance. 相似文献
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Kovarik Z Calić M Sinko G Bosak A Berend S Vrdoljak AL Radić B 《Chemico-biological interactions》2008,175(1-3):173-179
One of the therapeutic approaches to organophosphate poisoning is to reactivate AChE with site-directed nucleophiles such as oximes. However, pyridinium oximes 2-PAM, HI-6, TMB-4 and obidoxime, found as the most effective reactivators, have limiting reactivating potency in tabun poisoning. We tested oximes varying in the type of ring (pyridinium and/or imidazolium), the length and type of the linker between rings, and in the position of the oxime group on the ring to find more effective oximes to reactivate tabun-inhibited human erythrocyte AChE. Three of our tested pyridinium oximes K027, K048, K074, along with TMB-4, were the most promising for AChE reactivation. Promising oximes were further tested in vivo on tabun poisoned mice not only as antidotes in combination with atropine but also as pretreatment drug. Herein, we showed that a promising treatment in tabun poisoning by selected oximes and atropine could be improved if oximes are also used in pretreatment. Since the reactivating efficacy of the oximes in vitro corresponded to their therapeutic efficacy in vivo, it seems that pharmacological effect of these oximes is indeed primarily related to the reactivation of tabun-phosphorylated AChE. 相似文献
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Ljubojević S Lipozencić J Grgec DL Prstacić R Skerlev M Mokos ZB 《Collegium antropologicum》2008,32(3):989-997
Genital human papillomavirus (HPV) infections are among the most common sexually transmitted diseases. HPV is associated with a spectrum of diseases ranging from benign vulgar verrucae and condylomata accuminata to malignant cancers of the cervix, vulva, anus and penis. Genital HPV is in most cases transmitted sexually, but non-sexual routes of transmission, such as perinatal and autoinoculation, are possible. Men can be a reservoir of the virus that lives in latent or subclinical form on genital mucosa. Such an asymptomatic infection may be an oncogenic factor in the development of cervical cancer Colposcopic examination of the genitalia after the application of 3-5% acetic acid is a reliable method for the identification of subclinical HPV infection. Successful therapy of anogenital warts is characterized by their complete clearance, as well as by the lack of recurrence. Current treatments do not reliably eradicate HPV infections. The diagnosis and therapy of HPV infection in men is potentially beneficial because the eradication of penile HPV infection may decrease the reservoir of the virus. 相似文献
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Zagrovic B Gattin Z Lau JK Huber M van Gunsteren WF 《European biophysics journal : EBJ》2008,37(6):903-912
We have studied two different beta-peptides in methanol using explicit solvent molecular dynamics simulations and the GROMOS 53A6 force field: a heptapeptide (peptide 1) expected to form a left-handed 3(14)-helix, and a hexapeptide (peptide 2) expected to form a beta-hairpin in solution. Our analysis has focused on identifying and analyzing the stability of the dominant secondary structure conformations adopted by the peptides, as well as on comparing the experimental NOE distance upper bounds and 3J-coupling values with their counterparts calculated on the basis of the simulated ensembles. Moreover, we have critically compared the present results with the analogous results obtained with the GROMOS 45A3 (peptide 1) and 43A1 (peptide 2) force fields. We conclude that within the limits of conformational sampling employed here, the GROMOS 53A6 force field satisfactorily reproduces experimental findings regarding the behavior of short beta-peptides, with accuracy that is comparable to but not exceeding that of the previous versions of the force field. GCE legend Conformational clustering analysis of the simulated ensemble of a ss-hexapeptide with two different simulation setups (a and b). The central members of all of the clusters populating more than 5% of all of the structures are shown, together with the most dominant hydrogen bonds and the corresponding percentages of cluster members containing them. 相似文献
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Bambuterol, a dimethylcarbamate, carbamoylates butyrylcholinesterase (BChE; EC 3.1.1.8). The carbamoylated enzyme is not very stable and the final product of the two-step hydrolysis is a bronchodilator drug, terbutaline (1-(3,5-dihydroxyphenyl)-2-t-butylamino-ethanol sulphate). Both bambuterol and terbutaline inhibit BChE, but their affinities differ in human serum BChE variants (U, A, F, K and S) due to their positive charge. Bambuterol inhibition rate constants for the homozygous usual (UU), Kalow (KK), fluoride-resistant (FF) or atypical (AA) variant ranged from 4.4 to 0.085min (-1)microM(-1). Terbutaline showed competitive reversible inhibition for all BChE variants. The dissociation constants for UU, FF and AA homozygotes were 0.18, 0.31 and 3.3 mM, respectively. The inhibition rate or dissociation constants for heterozygotes were distributed between the respective constants for the corresponding homozygotes. A 50-fold difference in inhibition between the UU and AA enzyme might affect terbutaline release in humans. The affinity of all studied BChE variants for terbutaline was low, which suggests that terbutaline originating from bambuterol hydrolysis should not affect the hydrolysis of bambuterol by BChE. 相似文献
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Salt stress and plasma-membrane fluidity in selected extremophilic yeasts and yeast-like fungi 总被引:3,自引:0,他引:3
We have investigated changes in plasma-membrane fluidity in relation to NaCl concentrations in yeasts and yeast-like fungi that were isolated from either subglacial ice or hypersaline waters. In both of these natural environments, these organisms are exposed to low water activity, due to either high NaCl concentrations or low temperatures. Our data indicate that the fluidity of the plasma membrane can be used as an indicator of fitness for survival in extreme environments. Fungi that can survive in such extreme environments, such as Hortaea werneckii in the hypersaline waters of salterns, and Cryptococcus liquefaciens in subglacial environments, showed similar profiles of plasma-membrane fluidity in response to raised salinity. The same was seen for ubiquitous fungi, which are generally adapted for different types of stress, such as Aureobasidium pullulans and Rhodotorula mucilaginosa. Representatives of both of these groups modulated their plasma-membrane fluidity differently. When salinity exceeded their optimal range, the ubiquitous stress-tolerant species (A. pullulans, Rh. mucilaginosa) showed increased plasma-membrane fluidity, whereas in the dominant extremophiles (H. werneckii, Cr. liquefaciens), it decreased. On the other hand, the plasma membranes of the fungi with a narrow ecological amplitude (Arctic A. pullulans and Rhodosporium diobovatum) showed different responses. 相似文献
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Kubale V Abramović Z Pogacnik A Heding A Sentjurc M Vrecl M 《Cell and tissue research》2007,330(2):231-245
This study was focused on the relationship between the plasma-membrane localization of neurokinin-1 receptor (NK1-R) and its
endocytic and signaling properties. First, we employed electron paramagnetic resonance (EPR) to study the domain structure
of HEK-293 cells and NK1-R microlocalization. EPR spectra and the GHOST condensation routine demonstrated that NK1-R was distributed
in a well-ordered domain of HEK-293 cells possibly representing lipid raft/caveolae microdomains, whereas the impairment of
caveolae changed the NK1-R plasma-membrane distribution. Internalization and second messenger assays combined with bioluminescence
resonance energy transfer were employed subsequently to evaluate the functional importance of the NK1-R microlocalization
in lipid raft/caveolae microdomains. The internalization pattern was delineated through the use of dominant-negative mutants
(DNM) of caveolin-1 S80E (Cav1 S80E), dynamin-1 K44A (Dyn K44A), and β-arrestin (β-arr 319–418) and by means of cell lines
that expressed various endogenous levels of β-arrestins. NK1-R displayed rapid internalization that was substantially reduced
by DNMs of dynamin-1 and β-arrestin and even more profoundly in cells lacking both β-arrestin1 and β-arrestin2. These internalization
data were highly suggestive of the predominant use of the clathrin-mediated pathway by NK1-R, even though NK1-R tended to
reside constitutively in lipid raft/caveolae microdomains. Evidence was also obtained that the proper clustering of the receptor
in these microdomains was important for effective agonist-induced NK1-R signaling and for its interaction with β-arrestin2.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
This work was supported by the Slovenian Ministry of Higher Education, Science, and Technology (grant number 0406-007) and
a Slovenian-Danish collaboration grant (BI-DK/06-07-007). 相似文献
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Zrinka Raguz Nakic Gerhard Seisenbacher Francesc Posas Uwe Sauer 《BMC systems biology》2015,10(1):104