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991.
Smith BK Jain SS Rimbaud S Dam A Quadrilatero J Ventura-Clapier R Bonen A Holloway GP 《The Biochemical journal》2011,437(1):125-134
FAT/CD36 (fatty acid translocase/Cluster of Differentiation 36), a plasma membrane fatty-acid transport protein, has been found on mitochondrial membranes; however, it remains unclear where FAT/CD36 resides on this organelle or its functional role within mitochondria. In the present study, we demonstrate, using several different approaches, that in skeletal muscle FAT/CD36 resides on the OMM (outer mitochondrial membrane). To determine the functional role of mitochondrial FAT/CD36 in this tissue, we determined oxygen consumption rates in permeabilized muscle fibres in WT (wild-type) and FAT/CD36-KO (knockout) mice using a variety of substrates. Despite comparable muscle mitochondrial content, as assessed by unaltered mtDNA (mitochondrial DNA), citrate synthase, β-hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase complex IV and respiratory capacities [maximal OXPHOS (oxidative phosphorylation) respiration] in WT and KO mice, palmitate-supported respiration was 34% lower in KO animals. In contrast, palmitoyl-CoA-supported respiration was unchanged. These results indicate that FAT/CD36 is key for palmitate-supported respiration. Therefore we propose a working model of mitochondrial fatty-acid transport, in which FAT/CD36 is positioned on the OMM, upstream of long-chain acyl-CoA synthetase, thereby contributing to the regulation of mitochondrial fatty-acid transport. We further support this model by providing evidence that FAT/CD36 is not located in mitochondrial contact sites, and therefore does not directly interact with carnitine palmitoyltransferase-I as original proposed. 相似文献
992.
Basu A Jain P Sarkar P Gangodkar S Deshpande D Ganti K Shetty S Ghosh K 《FEMS immunology and medical microbiology》2011,62(2):140-147
Dengue virus (DENV) infection of human endothelial cells has been implicated in the pathobiology of dengue hemorrhagic fever and dengue shock syndrome. However, the mechanisms by which DENV infections alter the functional physiology of endothelial cells remain incompletely understood. In the present study, we examined the susceptibility of a human liver sinusoidal endothelial cell line SK Hep1 to all four serotypes of DENV and studied the effect of the virus on in vitro angiogenesis. All four serotypes of DENV could infect the SK Hep1 cells, but showed variable cytopathic effects, the most pronounced being that of DENV-2. Electron microscopy of the infected cells showed significant ultrastructural changes. In vitro angiogenesis assays on DENV-2 exposed SK Hep1 cells in the matrigel system showed inhibition compared with the controls. Importantly, transfection and transient expression of the DENV-2 envelope glycoprotein (E) in these cells showed drastic alterations in cell shapes and the E protein could be localized by fluorescence microscopy in terminal knob-like structures. Therefore, SK Hep1, a human hepatic sinusoid-derived endothelial cell line, may constitute a potential model to study DENV-endothelial cell interactions in vitro, especially towards understanding the possible virus-induced changes in hepatic endothelium and its role in disease pathogenesis. 相似文献
993.
The demand in the field of medical diagnostics for simple, cost efficient and disposable devices is growing. Here, we present a label free, all-polymer electrochemical biosensor for detection of acute viral disease. The dynamics of a viral infection in human cell culture was investigated in a micro fluidic system on conductive polymer PEDOT:TsO microelectrodes by electrochemical impedance spectroscopy and video time lapse microscopy. Employing this sensitive, real time electrochemical technique, we could measure the immediate cell response to cytomegalovirus, and detect an infection within 3h, which is several hours before the cytopathic effect is apparent with conventional imaging techniques. Atomic force microscopy and scanning ion conductance microscopy imaging consolidate the electrochemical measurements by demonstrating early virus induced changes in cell morphology of apparent programmed cell death. 相似文献
994.
Hong Lim Sheh Ibrahim Darah Kassim Jain 《World journal of microbiology & biotechnology》2011,27(11):2737-2740
World Journal of Microbiology and Biotechnology - Rhizophora apiculata is a common mangrove tree in Malaysia. The bark of this tree has been reported to contain a chemical constituent such as... 相似文献
995.
Oxidative stress has been implicated as a contributor to both the onset and the progression of diabetes and its associated complications. Some of the consequences of an oxidative environment are the development of insulin resistance, β-cell dysfunction, impaired glucose tolerance, and mitochondrial dysfunction, which can lead ultimately to the diabetic disease state. Experimental and clinical data suggest an inverse association between insulin sensitivity and ROS levels. Oxidative stress can arise from a number of different sources, whether disease state or lifestyle, including episodes of ketosis, sleep restriction, and excessive nutrient intake. Oxidative stress activates a series of stress pathways involving a family of serine/threonine kinases, which in turn have a negative effect on insulin signaling. More experimental evidence is needed to pinpoint the mechanisms contributing to insulin resistance in both type 1 diabetics and nondiabetic individuals. Oxidative stress can be reduced by controlling hyperglycemia and calorie intake. Overall, this review outlines various mechanisms that lead to the development of oxidative stress. Intervention and therapy that alter or disrupt these mechanisms may serve to reduce the risk of insulin resistance and the development of diabetes. 相似文献
996.
Pandya V Jain M Chakrabarti G Soni H Parmar B Chaugule B Patel J Joshi J Joshi N Rath A Raviya M Shaikh M Sairam KV Patel H Patel P 《Bioorganic & medicinal chemistry letters》2011,21(19):5701-5706
Two novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed as potent PAI-1 inhibitors using hybridization and conformational restriction strategy in the tiplaxtinin and piperazine chemo types. The lead compounds 5a, 6c, and 6e exhibited potent PAI-1 inhibitory activity and favorable oral bioavailability in the rodents. 相似文献
997.
Cerdeira LT Schneider MP Pinto AC de Almeida SS dos Santos AR Barbosa EG Ali A Aburjaile FF de Abreu VA Guimarães LC Soares Sde C Dorella FA Rocha FS Bol E Gomes de Sá PH Lopes TS Barbosa MS Carneiro AR Jucá Ramos RT Coimbra NA Lima AR Barh D Jain N Tiwari S Raja R Zambare V Ghosh P Trost E Tauch A Miyoshi A Azevedo V Silva A 《Journal of bacteriology》2011,193(24):7025-7026
In this work, we report the whole-genome sequence of Corynebacterium pseudotuberculosis bv. equi strain CIP 52.97 (Collection Institut Pasteur), isolated in 1952 from a case of ulcerative lymphangitis in a Kenyan horse, which has evidently caused significant losses to agribusiness. Therefore, obtaining this genome will allow the detection of important targets for postgenomic studies, with the aim of minimizing problems caused by this microorganism. 相似文献
998.
This work examined the novel hypothesis that reduced levels of H(2)S or L-cysteine (LC) play a role in the impaired glucose metabolism seen in diabetes. 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) in the presence or absence of LC or H(2)S. Both LC and H(2)S treatments caused an increase in phosphatidylinositol-3,4,5 trisphosphate (PIP3), AKT phosphorylation, and glucose utilization in HG-treated cells. The effect of LC on PIP3 and glucose utilization was prevented by propargylglycine, an inhibitor of cystathionine γ-lyase that catalyzes H(2)S formation from LC. This demonstrates that H(2)S mediates the effect of LC on increased PIP3 and glucose utilization. H(2)S and LC caused phosphatidylinositol 3-kinase activation and PTEN inhibition. Treatment with LC, H(2)S, or PIP3 increased the phosphorylation of IRS1, AKT, and PKCζ/λ as well as GLUT4 activation and glucose utilization in HG-treated cells. This provides evidence that PIP3 is involved in the increased glucose utilization observed in cells supplemented with LC or H(2)S. Comparative signal silencing studies with siAKT2 or siPKCζ revealed that PKCζ phosphorylation is more effective for the GLUT4 activation and glucose utilization in LC-, H(2)S-, or PIP3-treated cells exposed to HG. This is the first report to demonstrate that H(2)S or LC can increase cellular levels of PIP3, a positive regulator of glucose metabolism. The PIP3 increase is mediated by PI3K activation and inhibition of PTEN but not of SHIP2. This study provides evidence for a molecular mechanism by which H(2)S or LC can up-regulate the insulin-signaling pathways essential for maintenance of glucose metabolism. 相似文献
999.
Diethyltin(methoxy)methanesulfonate reacts readily with equimolar amount of t-butylphosphonic acid (RT, 8-10 h) in moist dichloromethane and methanol to afford [(Et2Sn)6(O3PBut)4(OSO2Me)4·CH2Cl2]n (1) and [(Et2Sn)6(O3PBut)4(OSO2Me)4·2H2O]n (2), respectively. The identity of these compounds has been established by IR, multinuclear (1H, 13C, 31P and 119Sn) NMR as well as X-ray crystallographic studies. Despite apparent similarity in the composition, a marked difference in the structural motifs between 1 and 2 is evident in the solid state. For 1, the formation of three-dimensional self- assembly results from μ3-phosphonate and μ2, μ3-sulfonate binding modes and exhibits continuous channel of voids which are occupied by disordered CH2Cl2 molecules. In contrast, the sulfonate ligands in 2 act exclusively in μ2-fashion and hydrogen bonding interactions (O-H?O) between coordinated water molecules and methanesulfonate groups is significant in the construction of 3D supramolecular assembly. 相似文献
1000.
Hawkins O Verma B Lightfoot S Jain R Rawat A McNair S Caseltine S Mojsilovic A Gupta P Neethling F Almanza O Dooley W Hildebrand W Weidanz J 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(11):6607-6616
This report describes a novel HLA/peptide complex with potential prognostic and therapeutic roles for invasive breast cancer. Macrophage migration inhibitory factor (MIF) mediates inflammation and immunity, and MIF overexpression is observed in breast cancer. We hypothesized that the HLA class I of cancerous breast epithelial cells would present MIF-derived peptides. Consistent with this hypothesis, the peptide FLSELTQQL (MIF(19-27)) was eluted from the HLA-A*0201 (HLA-A2) of breast cancer cell lines. We posited that if this MIF(19-27)/HLA-A2 complex was exclusively found in invasive breast cancer, it could be a useful prognostic indicator. To assess the presentation of MIF peptides by the HLA of various cells and tissues, mice were immunized with the MIF(19-27)/HLA-A2 complex. The resulting mAb (RL21A) stained invasive ductal carcinoma (IDC) but not ductal carcinoma in situ, fibroadenoma, or normal breast tissues. RL21A did not stain WBCs (total WBCs) or normal tissues from deceased HLA-A2 donors, substantiating the tumor-specific nature of this MIF/HLA complex. As this MIF/HLA complex appeared specific to the surface of IDC, RL21A was tested as an immunotherapeutic for breast cancer in vitro and in vivo. In vitro, RL21A killed the MDA-MB-231 cell line via complement and induction of apoptosis. In an in vivo orthotopic mouse model, administration of RL21A reduced MDA-MB-231 and BT-20 tumor burden by 5-fold and by >2-fold, respectively. In summary, HLA-presented MIF peptides show promise as prognostic cell surface indicators for IDC and as targets for immunotherapeutic intervention. 相似文献