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排序方式: 共有415条查询结果,搜索用时 15 毫秒
41.
Michelle Pacholec John E. Bleasdale Boris Chrunyk David Cunningham Declan Flynn Robert S. Garofalo David Griffith Matt Griffor Pat Loulakis Brandon Pabst Xiayang Qiu Brian Stockman Venkataraman Thanabal Alison Varghese Jessica Ward Jane Withka Kay Ahn 《The Journal of biological chemistry》2010,285(11):8340-8351
42.
43.
Much discussion has recently centred around the biochemical mechanisms by which ceramide is produced in signalling pathways. Since ceramide is virtually insoluble in aqueous solutions, the biological effects of ceramide should be considered in the context of its generation within the membrane lipid bilayer. To this end, we now summarize recent data describing some biophysical properties of ceramide that are of relevance for understanding the mode of ceramide action as a second messenger, and, as a consequence, how the site(s) of ceramide generation might impact upon its role in signalling. 相似文献
44.
Lipid aldehydes generated by lipid peroxidation induce cell damage and inflammation. Recent evidence indicates that γ-ketoaldehydes (isolevuglandins, IsoLGs) form inflammatory mediators by modifying the ethanolamine headgroup of phosphatidylethanolamines (PEs). To determine if other species of aldehyde-modified PEs (al-PEs) with inflammatory bioactivity were generated by lipid peroxidation, we oxidized liposomes containing arachidonic acid and characterized the resulting products. We detected PE modified by IsoLGs, malondialdehyde (MDA), and 4-hydroxynonenal (HNE), as well as a novel series of N-acyl-PEs and N-carboxyacyl-PEs in these oxidized liposomes. These al-PEs were also detected in high-density lipoproteins exposed to myeloperoxidase. When we tested the ability of al-PEs to induce THP-1 monocyte adhesion to cultured endothelial cells, we found that PEs modified by MDA, HNE, and 4-oxononenal induced adhesion with potencies similar to those of PEs modified by IsoLGs (~2μM). A commercially available medium-chain N-carboxyacyl-PE (C11:0CAPE) also stimulated adhesion, whereas C4:0CAPE and N-acyl-PEs did not. PEs modified by acrolein or by glucose were only partial agonists for adhesion. These studies indicate that lipid peroxidation generates a large family of al-PEs, many of which have the potential to drive inflammation. 相似文献
45.
Raghav PK Verma YK Gangenahalli GU 《International journal of biological macromolecules》2012,50(3):796-814
Bcl-2 (B cell lymphoma-2) is an anti-apoptotic member of Bcl-2 family and its overexpression causes development of several types of cancer. The BH3 domain of pro-apoptotic and BH3-only proteins is capable of binding to Bcl-2 protein to induce apoptosis. This binding is the basis for the development of novel anticancer drug which would likely antagonize Bcl-2 overexpression. In this study we have identified BH3 domain of Bax (Bax BH3) as potentially the best Bcl-2 antagonist by performing docking of BH3 peptides (peptides representing BH3 domain of pro-apoptotic and BH3-only proteins) into the Bcl-2 hydrophobic groove formed by BH3, BH1 and BH2 domains (also referred as BH3 cleft). To predict the best small antagonist for Bcl-2, three groups of small peptides (pentapeptide, tetrapeptide and tripeptide) were designed and screened against Bcl-2 which revealed the structural importance of a set of residues playing a vital role in interaction with Bcl-2. The docking and scoring function identified KRIG and KRI as specific peptides among the screened small peptides responsible for Bcl-2 neutralization and would induce apoptosis. The applied pharmacokinetic and pharmacological filters to all small peptides signify that only IGD has drug-like properties and displayed good oral bioavailability. However, the obtained binding affinity of IGD to Bcl-2 was diminutive. Hence deprotonation, amidation, acetylation, benzoylation, benzylation, and addition of phenyl, deoxyglucose and glucose fragments were performed to increase the binding affinity and to prevent its rapid degradation. Benzoylated IGD tripeptide (IGD(bzo)) was observed to have increased binding affinity than IGD with acceptable pharmacokinetic filters. In addition, stability of Bcl-2/IGD(bzo) complex was validated by Molecular Dynamics (MD) simulations revealing improved binding energy, salt bridges and strong interaction energies. This study suggests a new molecule that inhibits Bcl-2 associated cancer/tumor regression. 相似文献
46.
James AW Zara JN Corselli M Chiang M Yuan W Nguyen V Askarinam A Goyal R Siu RK Scott V Lee M Ting K Péault B Soo C 《Journal of visualized experiments : JoVE》2012,(63):e2952
Human perivascular stem cells (PSCs) can be isolated in sufficient numbers from multiple tissues for purposes of skeletal tissue engineering. PSCs are a FACS-sorted population of 'pericytes' (CD146+CD34-CD45-) and 'adventitial cells' (CD146-CD34+CD45-), each of which we have previously reported to have properties of mesenchymal stem cells. PSCs, like MSCs, are able to undergo osteogenic differentiation, as well as secrete pro-osteogenic cytokines. In the present protocol, we demonstrate the osteogenicity of PSCs in several animal models including a muscle pouch implantation in SCID (severe combined immunodeficient) mice, a SCID mouse calvarial defect and a femoral segmental defect (FSD) in athymic rats. The thigh muscle pouch model is used to assess ectopic bone formation. Calvarial defects are centered on the parietal bone and are standardly 4 mm in diameter (critically sized). FSDs are bicortical and are stabilized with a polyethylene bar and K-wires. The FSD described is also a critical size defect, which does not significantly heal on its own. In contrast, if stem cells or growth factors are added to the defect site, significant bone regeneration can be appreciated. The overall goal of PSC xenografting is to demonstrate the osteogenic capability of this cell type in both ectopic and orthotopic bone regeneration models. 相似文献
47.
B-cell lymphoma (Bcl-2) protein is an anti-apoptotic member of the Bcl-2 family. It is functionally demarcated into four Bcl-2
homology (BH) domains: BH1, BH2, BH3, BH4, one flexible loop domain (FLD), a transmembrane domain (TM), and an X domain. Bcl-2’s
BH domains have clearly been elucidated from a structural perspective, whereas the conformation of FLD has not yet been predicted,
despite its important role in regulating apoptosis through its interactions with JNK-1, PKC, PP2A phosphatase, caspase 3,
MAP kinase, ubiquitin, PS1, and FKBP38. Many important residues that regulate Bcl-2 anti-apoptotic activity are present in
this domain, for example Asp34, Thr56, Thr69, Ser70, Thr74, and Ser87. The structural elucidation of the FLD would likely
help in attempts to accurately predict the effect of mutating these residues on the overall structure of the protein and the
interactions of other proteins in this domain. Therefore, we have generated an increased quality model of the Bcl-2 protein
including the FLD through modeling. Further, molecular dynamics (MD) simulations were used for FLD optimization, to predict
the flexibility, and to determine the stability of the folded FLD. In addition, essential dynamics (ED) was used to predict
the collective motions and the essential subspace relevant to Bcl-2 protein function. The predicted average structure and
ensemble of MD-simulated structures were submitted to the Protein Model Database (PMDB), and the Bcl-2 structures obtained
exhibited enhanced quality. This study should help to elucidate the structural basis for Bcl-2 anti-apoptotic activity regulation
through its binding to other proteins via the FLD. 相似文献
48.
L M Sayre D A Engelhart B Venkataraman M K Babu G D McCoy 《Biochemical and biophysical research communications》1991,179(3):1368-1376
Microsomal oxidation of 1-benzylpiperidine (1-BP) and its cis-2,6-dimethyl analog was studied to assess the involvement of endocyclic enamines, in equilibrium with the initially formed iminiums, in the metabolic activation of cyclic tertiary amines such as phencyclidine. Since the iminiums can be trapped with cyanide, the selective prevention by cyanide of the metabolic production of 1-benzyl-3-piperidone from 1-BP implicates the iminium in equilibrium with enamine as the source of this metabolite. In cases where iminium-enamine coupling is sterically prevented, the iminium in equilibrium with enamine species can be studied independently and are found to be more potent metabolism-dependent inactivators of cytochrome P-450 than are the corresponding parent amines. Possible mechanisms for biological oxidation of cyclic enamines to reactive intermediates are considered. 相似文献
49.
A series of phosphate esters derived from N-hydroxysuccinimide and 3-alkyl-N-hydroxysuccinimide have been synthesized and found to be potent time-dependent irreversible inhibitors of human leukocyte elastase (HLE). The observed inhibitory activity in this series of compounds correlated well with the known preference of HLE for substrates with small hydrophobic side chains. Maximum potency was reached when a favorable aromatic interaction involving a phenyl group present in the inhibitor and an aromatic residue located in the vicinity of the S2' subsite was operative. 31P NMR spectroscopy was used to probe the mechanism of action of these compounds. Direct evidence is presented in support of a mechanism involving phosphorylation of the active site serine. These compounds constitute a new class of hydrolytically stable phosphorylating agents. 相似文献
50.
An oxidative and salinity stress induced peroxisomal ascorbate peroxidase from Avicennia marina: Molecular and functional characterization 总被引:1,自引:0,他引:1
Kumaresan Kavitha Gayatri Venkataraman Ajay Parida 《Plant Physiology and Biochemistry》2008,46(8-9):794-804
APX (EC, 1.11.1.11) has a key role in scavenging ROS and in protecting cells against their toxic effects in algae and higher plants. A cDNA encoding a peroxisomal ascorbate peroxidase, Am-pAPX1, was isolated from salt stressed leaves of Avicennia marina (Forsk.) Vierh. by EST library screening and its expression in the context of various environmental stresses was investigated. Am-pAPX1 contains an ORF of 286 amino acids coding for a 31.4kDa protein. The C-terminal region of the Am-pAPX1 ORF has a putative transmembrane domain and a peroxisomal targeting signal (RKKMK), suggesting peroxisomal localization. The peroxisomal localization of Am-pAPX1 was confirmed by stable transformation of the GFP-(Ala)(10)-Am-pAPX1 fusion in tobacco. RNA blot analysis revealed that Am-pAPX1 is expressed in response to salinity (NaCl) and oxidative stress (high intensity light, hydrogen peroxide application and excess iron). The isolated genomic clone of Am-pAPX1 was found to contain nine exons. A fragment of 1616bp corresponding to the 5' upstream region of Am-pAPX1 was isolated by TAIL-PCR. In silico analysis of this sequence reveals the presence of putative light and abiotic stress regulatory elements. 相似文献