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Subsequent Degradation (subsequent + degradation)
Selected AbstractsUncompromised generation of a specific H-2DM-dependent peptide-MHC class,II complex from exogenous antigen in Leishmania mexicana -infected dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003Clare Abstract Leishmania infection inhibits the capacity of macrophages (M,) to present antigens to CD4+ T cells. Relocation of MHC class,II and H-2DM to the parasitophorous vacuole (PV) and their subsequent degradation by the parasite may contribute to this defect. Dendritic cells (DC) are critical for initiation of primary T cell responses. DC can process Leishmania antigen and elicit Leishmania -specific T cells, but it is unknown whether exposure to Leishmania impairs this capacity. In particular, it is not clear whether DC containing live parasites efficiently process and present antigens. We investigated the ability of mouse bone marrow-derived DC infected with L. mexicana to generate pigeon cytochrome,c (PCC) peptide-MHC class II complexes, using the mAb D4, which recognizes PCC89,104 H-2Ek, and the PCC-specific T cell hybridoma 2B4. We show that H-2DM-dependent complex generation is not compromised by infection and that complexes are fully recognized by specific T cells. We further show that in contrast to infected M,, in infected DC cytoplasmic H-2DM is not down-regulated and not relocated to the parasite-containing vacuole. This observation may explain the continued ability of infected DC to present PCC, and also indicates differences in the habitat of these intracellular parasites in DC compared to M,. [source] Regulation of Sprouty2 stability by mammalian Seven-in-Absentia homolog 2,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2007Robert J. Nadeau Abstract Mammalian Sprouty (Spry) gene expression is rapidly induced upon activation of the FGF receptor signaling pathway in multiple cell types including cells of mesenchymal and epithelial origin. Spry2 inhibits FGF-dependent ERK activation and thus Spry acts as a feedback inhibitor of FGF-mediated proliferation. In addition, Spry2 interacts with the ring-finger-containing E3 ubiquitin ligase, c-Cbl, in a manner that is dependent upon phosphorylation of Tyr55 of Spry2. This interaction results in the poly-ubiquitination and subsequent degradation of Spry2 by the proteasome. Here, we describe the identification of another E3 ubiquitin ligase, human Seven-in-Absentia homolog-2 (SIAH2), as a Spry2 interacting protein. We show by yeast two-hybrid analysis that the N-terminal domain of Spry2 and the ring finger domain of SIAH2 mediated this interaction. Co-expression of SIAH2 resulted in proteasomal degradation of Spry1, 2, and to a lesser extent Spry4. The related E3 ubiquitin-ligase, SIAH1, had little effect on Spry2 protein stability when co-expressed. Unlike c-Cbl-mediated degradation of Spry2, SIAH2-mediated degradation was independent of phosphorylation of Spry2 on Tyr55. Spry2 was also phosphorylated on Tyr227, and phosphorylation of this residue was also dispensable for SIAH2-mediated degradation of Spry2. Finally, co-expression of SIAH2 with Spry2 resulted in a rescue of FGF2-mediated ERK phosphorylation. These data suggest a novel mechanism whereby Spry2 stability is regulated in a manner that is independent of tyrosine phosphorylation, and provides an addition level of control of Spry2 protein levels. J. Cell. Biochem. 100: 151,160, 2007. © 2006 Wiley-Liss, Inc. [source] Twenty years of resolving the irresolvable: approaches to the fuelwood problem in KenyaLAND DEGRADATION AND DEVELOPMENT, Issue 3 2001I. Mahiri Abstract Resolving the fuelwood problem in Kenya has been the cause of many debates. A review of the literature reveals the changing emphasis on the cause and effect of the problem. The dominant focus links fuelwood consumption with environmental degradation. This view has been perpetuated and reinforced by the ,Woodfuel Gap' theory of supply and demand differentials, based on population growth. The demand mitigation has been addressed through the ,Fuelwood Orthodoxy' approach and energy technologies. This paper shows that deforestation, and subsequent degradation, has little to do with fuelwood consumption as much is extracted from outside the forest. Therefore, costly interventions of afforestation programmes have had little impact in addressing the issue. The locale-specificity of the fuelwood problem means there can be no simple, technical solution. The local nature of shortages means that national projections cannot capture the complex socio-economic and cultural issues. Such complexity and diversity of rural contexts demand that the rural energy problem cannot be treated in isolation from the equally pressing issues of poverty, labour, food, culture and values. Copyright © 2001 John Wiley & Sons, Ltd. [source] 6-Shogaol is more effective than 6-gingerol and curcumin in inhibiting 12- O -tetradecanoylphorbol 13-acetate-induced tumor promotion in miceMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 9 2010Hou Wu Abstract We previously reported that 6-shogaol strongly suppressed lipopolysaccharide-induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrate that topical application of 6-shogaol more effectively inhibited 12- O -tetradecanoylphorbol 13-acetate (TPA)-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-,B subunits. 6-Shogaol also reduced TPA-induced phosphorylation of I,B, and p65, and caused subsequent degradation of I,B,. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulate kinase1/2, p38 mitogen-activated protein kinase, JNK1/2, and phosphatidylinositol 3-kinase/Akt, which are upstream of nuclear factor-,B and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20,wk. Presented data reveal for the first time that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that 6-shogaol is a novel functional agent capable of preventing inflammation-associated tumorigenesis. [source] 6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophagesMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 12 2008Min-Hsiung Pan Abstract Ginger, the rhizome of Zingiber officinale, is a traditional medicine with carminative effect, antinausea, anti-inflammatory, and anticarcinogenic properties. In this study, we investigated the inhibitory effects of 6-shogaol and a related compound, 6-gingerol, on the induction of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with LPS. Western blotting and reverse transcription-PCR analyses demonstrated that 6-shogaol significantly blocked protein and mRNA expression of inducible NOS (iNOS) and COX-2 in LPS-induced macrophages. The in vivo anti-inflammatory activity was evaluated by a topical 12- O -tetradecanoylphorbol 13-acetate (TPA) application to mouse skin. When applied topically onto the shaven backs of mice prior to TPA, 6-shogaol markedly inhibited the expression of iNOS and COX-2 proteins. Treatment with 6-shogaol resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-,B (NF,B) subunit and the dependent transcriptional activity of NF,B by blocking phosphorylation of inhibitor ,B (I,B), and p65 and subsequent degradation of I,B,. Transient transfection experiments using NF,B reporter constructs indicated that 6-shogaol inhibits the transcriptional activity of NF,B in LPS-stimulated mouse macrophages. We found that 6-shogaol also inhibited LPS-induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2, but not p38 mitogen-activated protein kinase (MAPK). Taken together, these results show that 6-shogaol downregulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NF,B by interfering with the activation PI3K/Akt/I,B kinases IKK and MAPK. [source] Identification of heat-induced degradation products from purified betanin, phyllocactin and hylocerenin by high-performance liquid chromatography/electrospray ionization mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2005Kirsten M. Herbach Betanin, phyllocactin (malonylbetanin) and hylocerenin (3-hydroxy-3-methylglutarylbetanin) were isolated from purple pitaya (Hylocereus polyrhizus [Weber] Britton & Rose) juice, and their degradation products generated by heating at 85°C were subsequently monitored by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. Thermal degradation of phyllocactin and hylocerenin in purified solution excluding the alleged protective effects by the juice matrix is reported for the first time. Betanin was predominantly degraded by hydrolytic cleavage, while decarboxylation and dehydrogenation were of minor relevance. In contrast, hylocerenin showed a strong tendency to decarboxylation and dehydrogenation, hydrolytic cleavage of the aldimine bond occurring secondarily. Phyllocactin degradation was most complex because of additional decarboxylation of the malonic acid moiety as well as generation and subsequent degradation of betanin due to phyllocactin demalonylation. Upon prolonged heating, all betacyanins under observation formed degradation products characterized by an additional double bond at C2C3. Hydrolytic cleavage of the aldimine bond of phyllocactin and hylocerenin yielded previously unknown acylated cyclo -dopa derivatives traceable by positive ionization, while application of ESI(,) facilitated the detection of a glycosylated aminopropanal derivative and dopamine, which have never been described before as betanin degradation products. Copyright © 2005 John Wiley & Sons, Ltd. [source] Restoring Ecological Function to a Submerged Salt MarshRESTORATION ECOLOGY, Issue 2010Camille L. Stagg Impacts of global climate change, such as sea level rise and severe drought, have altered the hydrology of coastal salt marshes resulting in submergence and subsequent degradation of ecosystem function. A potential method of rehabilitating these systems is the addition of sediment-slurries to increase marsh surface elevation, thus ameliorating effects of excessive inundation. Although this technique is growing in popularity, the restoration of ecological function after sediment addition has received little attention. To determine if sediment subsidized salt marshes are functionally equivalent to natural marshes, we examined above- and belowground primary production in replicated restored marshes receiving four levels of sediment addition (29,42 cm North American Vertical Datum of 1988 [NAVD 88]) and in degraded and natural ambient marshes (4,22 cm NAVD 88). Moderate intensities of sediment-slurry addition, resulting in elevations at the mid to high intertidal zone (29,36 cm NAVD 88), restored ecological function to degraded salt marshes. Sediment additions significantly decreased flood duration and frequency and increased bulk density, resulting in greater soil drainage and redox potential and significantly lower phytotoxic sulfide concentrations. However, ecological function in the restored salt marsh showed a sediment addition threshold that was characterized by a decline in primary productivity in areas of excessive sediment addition and high elevation (>36 cm NAVD 88). Hence, the addition of intermediate levels of sediment to submerging salt marshes increased marsh surface elevation, ameliorated impacts of prolonged inundation, and increased primary productivity. However, too much sediment resulted in diminished ecological function that was equivalent to the submerged or degraded system. [source] | ||||||||||