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排序方式: 共有617条查询结果,搜索用时 46 毫秒
111.
Ponnappan S Ovaa H Ponnappan U 《The international journal of biochemistry & cell biology》2007,39(4):799-809
Aging, in the immune system, is characterized by a decreased ability to respond to exogenous insults, resulting in increased susceptibility to infections and blunted response to vaccination. While significant age-associated deficits in immune function have been documented, the underlying molecular mechanisms are still being investigated. A consistent decline in the proteolytic activity of the proteasome has been demonstrated with advancing age, implicating an important role for the proteasome in immune senescence, by studies that largely employed proteasome-enriched preparations from cell lysates. With the availability of novel cell permeable active site probes designed specifically for assaying proteasomal activity in live cells, we now confirm our earlier data demonstrating lower catalytic activity of the proteasome in primary human T cells obtained from the elderly when compared to those from young donors. Loss in proteasomal catalytic activity translated into a loss in functional activity, as was observed in a degradation assay employing an ubiquitinated protein substrate, Ub-IkappaBalpha. Unlike fluorogenic peptide substrates, use of ubiquitinated protein substrates not only confer greater stringency in terms of proteasomal hydrolysis, but also involve the participation of the 19S regulatory component. This age-associated loss in proteasomal activity is accompanied by alteration in the levels of catalytic, structural and regulatory subunits, with no change in that of the 11S activator or the inhibitor PAAF1. Oxidative modification, such as carbonylation and lipid-peroxidation, of proteasomal subunits was also detected in T cells from the elderly. Thus, oxidative modification and lower levels of proteasomal subunits contribute to decreased proteolytic activity during immune-senescence. 相似文献
112.
Robertson SL Smedley JG Singh U Chakrabarti G Van Itallie CM Anderson JM McClane BA 《Cellular microbiology》2007,9(11):2734-2755
Clostridium perfringens enterotoxin (CPE) binds to host cell receptors, forming a small complex precursor for two large complexes reportedly having molecular masses of approximately 155 or approximately 200 kDa. Formation of the approximately 155 kDa complex causes a Ca(2+) influx that leads to apoptosis or oncosis. CPE complex composition is currently poorly understood, although occludin was identified in the approximately 200 kDa complex. The current study used heteromer gel shift analysis to show both CPE large complexes contain six CPE molecules. Ferguson plots and size exclusion chromatography re-sized the approximately 155 and approximately 200 kDa complexes as approximately 425-500 kDa and approximately 550-660 kDa respectively. Co-immunoprecipitation and electroelution studies demonstrated both CPE-binding and non-CPE-binding claudins are associated with all three CPE complexes in Caco-2 cells and with small complex and approximately 425-500 kDa complex of claudin 4 transfectants. Fibroblast transfectants expressing claudin 4 or C-terminal truncated claudin 4 were CPE-sensitive and formed the approximately 425 kDa complex, indicating claudin-induced cell signalling is not required for CPE action and that expression of a single receptor claudin suffices for approximately 425-500 kDa CPE complex formation. These results identify CPE as a unique toxin that combines with tight junction proteins to form high-molecular-mass hexameric pores and alter membrane permeability. 相似文献
113.
Ke Wang Zhifen Yang Xu Liu Kai Mao Usha Nair Daniel J. Klionsky 《The Journal of biological chemistry》2012,287(45):37964-37972
Macroautophagy (hereafter autophagy) is a degradative cellular pathway that protects eukaryotic cells from stress, starvation, and microbial infection. This process must be tightly controlled because too little or too much autophagy can be deleterious to cellular physiology. The phosphatidylinositol (PtdIns) 3-kinase Vps34 is a lipid kinase that regulates autophagy, but the role of other PtdIns kinases has not been examined. Here we demonstrate a role for PtdIns 4-kinases and PtdIns4P 5-kinases in selective and nonselective types of autophagy in yeast. The PtdIns 4-kinase Pik1 is involved in Atg9 trafficking through the Golgi and is involved in both nonselective and selective types of autophagy, whereas the PtdIns4P 5-kinase Mss4 is specifically involved in mitophagy but not nonselective autophagy. Our data indicate that phosphoinositide kinases have multiple roles in the regulation of autophagic pathways. 相似文献
114.
Usha Gundimeda Thomas H. McNeill Albert A. Elhiani Jason E. Schiffman David R. Hinton Rayudu Gopalakrishna 《The Journal of biological chemistry》2012,287(41):34694-34708
As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKCϵ from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKCϵ and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKCϵ, resulting in preconditioning against cell death induced by OGD/R. 相似文献
115.
116.
Subhrangshu Guhathakurta Asem Surindro Singh Swagata Sinha Anindita Chatterjee Shabina Ahmed Saurabh Ghosh Rajamma Usha 《Neurochemistry international》2009,55(8):754-759
Several studies suggest involvement of serotoninergic system in the pathophysiology of Autism Spectrum Disorder (ASD). The 5-HT receptor binding studies using 3H-lysergic acid diethylamide (3H-LSD) and linkage analysis provided evidences to consider HTR2A as a potential candidate gene for ASD. The three SNPs, −1438A/G (rs6311), 102T/C (rs6313) and 1354C/T (rs6314) of HTR2A have been well studied in the etiology of various neuropsychiatric disorders. But studies on association of this gene with ASD are limited to two reports from American and Korean populations. Additionally there are reports, which demonstrated paternal imprinting of HTR2A with expression from only one allele. So far no reports are available on HTR2A and its association with any neuropsychiatric disorders from Indian population. Therefore, the present study investigates association of the above mentioned three markers of HTR2A with ASD in Indian population using population and family-based approaches. The study also deals with allelic expression pattern of HTR2A in Peripheral Blood Leukocytes (PBLs) to understand the parental imprinting status. The genotyping analyses were carried out for probands, parents and controls. The subsequent association analyses did not show association of these markers with ASD. So, HTR2A is unlikely to be a genetic marker for ASD in Indian population. The expression analyses showed absence of monoallelic expression, suggesting lack of parental imprinting of HTR2A gene. However, we noticed methylation of the CpG sites at −1438A/G and 102T/C loci of HTR2A gene. Further bioinformatics analysis revealed absence of CpG islands in the promoter of the gene supporting biallelic expression pattern of HTR2A in PBLs. 相似文献
117.
Wajahatullah Khan Usha P. Rayirath Sowmyalakshmi Subramanian Mundaya N. Jithesh Prasanth Rayorath D. Mark Hodges Alan T. Critchley James S. Craigie Jeff Norrie Balakrishan Prithiviraj 《Journal of Plant Growth Regulation》2009,28(4):386-399
Marine algal seaweed species are often regarded as an underutilized bioresource, many have been used as a source of food,
industrial raw materials, and in therapeutic and botanical applications for centuries. Moreover, seaweed and seaweed-derived
products have been widely used as amendments in crop production systems due to the presence of a number of plant growth-stimulating
compounds. However, the biostimulatory potential of many of these products has not been fully exploited due to the lack of
scientific data on growth factors present in seaweeds and their mode of action in affecting plant growth. This article provides
a comprehensive review of the effect of various seaweed species and seaweed products on plant growth and development with
an emphasis on the use of this renewable bioresource in sustainable agricultural systems. 相似文献
118.
Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice 总被引:3,自引:0,他引:3
Xin Wang Raghavendra Pralhada Rao Teresa Kosakowska-Cholody M. Athar Masood Eileen Southon Helin Zhang Cyril Berthet Kunio Nagashim Timothy K. Veenstra Lino Tessarollo Usha Acharya Jairaj K. Acharya 《The Journal of cell biology》2009,184(1):143-158
Ceramide transfer protein (CERT) functions in the transfer of ceramide from the endoplasmic reticulum (ER) to the Golgi. In this study, we show that CERT is an essential gene for mouse development and embryonic survival and, quite strikingly, is critical for mitochondrial integrity. CERT mutant embryos accumulate ceramide in the ER but also mislocalize ceramide to the mitochondria, compromising their function. Cells in mutant embryos show abnormal dilation of the ER and degenerating mitochondria. These subcellular changes manifest as heart defects and cause severely compromised cardiac function and embryonic death around embryonic day 11.5. In spite of ceramide accumulation, CERT mutant mice do not die as a result of enhanced apoptosis. Instead, cell proliferation is impaired, and expression levels of cell cycle–associated proteins are altered. Individual cells survive, perhaps because cell survival mechanisms are activated. Thus, global compromise of ER and mitochondrial integrity caused by ceramide accumulation in CERT mutant mice primarily affects organogenesis rather than causing cell death via apoptotic pathways. 相似文献
119.
Glycoproteins (GPs) were visualised histochemically in the secretory cells – the mucous goblet cells (the type A and the type B), the serous goblet cells, the club cells and the epithelial cells in the gill epithelium of Rita rita. The type A mucous goblet cells, the type B mucous goblet cells and the epithelial cells elaborate GPs with oxidizable vicinal diols and GPs with sialic acid residue without O-acyl substitution. In addition, GPs with O-sulphate esters are elaborated by the type A and GPs with O-acyl sugars by the type B mucous goblet cells. GPs are absent in the serous goblet cells and are with oxidizable vicinal diols in low moieties in the club cells. The analysis of the results elucidates interesting differences in the composition and concentration of GPs in the mucus elaborated by the epithelium of the gill arches and the gill rakers; and the gill filaments and the secondary lamellae indicating the potential importance of the glycoproteins at these locations. GPs elaborated on the surfaces of the gill arches and the gill rakers could be associated to assist in feeding activities and on the surfaces of the gill filaments and the secondary lamellae in the respiratory activity. 相似文献
120.
Andrew E. Teschendorff Usha Menon Aleksandra Gentry-Maharaj Susan J. Ramus Simon A. Gayther Sophia Apostolidou Allison Jones Matthias Lechner Stephan Beck Ian J. Jacobs Martin Widschwendter 《PloS one》2009,4(12)