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51.
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53.
A biochemical investigation of arabinogalactan proteins (AGPs) in Physcomitrella
patens was undertaken with particular emphasis on the glycan chains. Following homogenization and differential centrifugation of
moss gametophytes, AGPs were obtained by Yariv phenylglycoside-induced precipitation from the soluble, microsomal membrane,
and cell wall fractions. Crossed-electrophoresis indicated that each of these three AGP fractions was a mixture of several
AGPs. The soluble AGP fraction was selected for further separation by anion-exchange and gel-permeation chromatography. The
latter indicated molecular masses of ∼100 and 224 kDa for the two major soluble AGP subfractions. The AGPs in both of these
subfractions contained the abundant (1,3,6)-linked galactopyranosyl residues, terminal arabinofuranosyl residues, and (1,4)-linked
glucuronopyranosyl residues that are typical of many angiosperm AGPs. Unexpectedly, however, the moss AGP glycan chains contained
about 15 mol% terminal 3-O-methyl-l-rhamnosyl residues, which have not been found in angiosperm AGPs. This unusual and relatively nonpolar sugar, also called
l-acofriose, is likely to have considerable effects on the overall polarity of Physcomitrella AGPs. A review of the literature indicates that the capacity to synthesize polymers containing 3-O-methyl-l-rhamnosyl residues is present in a variety of bacteria, algae and lower land plants but became less common through evolution
to the extent that this sugar has been found in only a few species of angiosperms where it occurs as a single residue on steroidal
glycosides. 相似文献
54.
He M Horuk R Moochhala SM Bhatia M 《American journal of physiology. Gastrointestinal and liver physiology》2007,292(4):G1173-G1180
Sepsis is a complex clinical syndrome resulting from a harmful host inflammatory response to infection. Chemokines and their receptors play a key role in the pathogenesis of sepsis. BX471 is a potent nonpeptide CC chemokine receptor-1 (CCR1) antagonist in both human and mouse. The aim of the present study was to evaluate the effect of prophylactic and therapeutic treatment with BX471 on cecal ligation and puncture-induced sepsis in the mouse and to investigate the underlying mechanisms. In sepsis induced by cecal ligation and puncture, treatment with BX471 significantly protected mice against lung and liver injury by attenuating MPO activity, an indicator of neutrophil recruitment in lungs and livers and attenuating lung and liver morphological changes in histological sections. Blocking CCR1 by BX471 also downregulated ICAM-1, P-selectin, and E-selectin expression at mRNA and protein levels in lungs and livers compared with placebo-treated groups. These findings suggest that blockage of CCR1 by specific antagonist may represent a promising strategy to prevent disease progression in sepsis. 相似文献
55.
Mitogen-activated protein kinase kinase-4 promotes cell survival by decreasing PTEN expression through an NF kappa B-dependent pathway 总被引:2,自引:0,他引:2
Xia D Srinivas H Ahn YH Sethi G Sheng X Yung WK Xia Q Chiao PJ Kim H Brown PH Wistuba II Aggarwal BB Kurie JM 《The Journal of biological chemistry》2007,282(6):3507-3519
56.
Qanungo S Starke DW Pai HV Mieyal JJ Nieminen AL 《The Journal of biological chemistry》2007,282(25):18427-18436
In murine embryonic fibroblasts, N-acetyl-L-cysteine (NAC), a GSH generating agent, enhances hypoxic apoptosis by blocking the NFkappaB survival pathway (Qanungo, S., Wang, M., and Nieminen, A. L. (2004) J. Biol. Chem. 279, 50455-50464). Here, we examined sulfhydryl modifications of the p65 subunit of NFkappaB that are responsible for NFkappaB inactivation. In MIA PaCa-2 pancreatic cancer cells, hypoxia increased p65-NFkappaB DNA binding and NFkappaB transactivation by 2.6- and 2.8-fold, respectively. NAC blocked these events without having an effect on p65-NFkappaB protein levels and p65-NFkappaB nuclear translocation during hypoxia. Pharmacological inhibition of the NFkappaB pathway also induced hypoxic apoptosis, indicating that the NFkappaB signaling pathway is a major protective mechanism against hypoxic apoptosis. In cell lysates after hypoxia and treatment with N-ethylmaleimide (thiol alkylating agent), dithiothreitol (disulfide reducing agent) was not able to increase binding of p65-NFkappaB to DNA, suggesting that most sulfhydryls in p65-NFkappaB protein were in reduced and activated forms after hypoxia, thereby being blocked by N-ethylmaleimide. In contrast, with hypoxic cells that were also treated with NAC, dithiothreitol increased p65-NFkappaB DNA binding. Glutaredoxin (GRx), which specifically catalyzes reduction of protein-SSG mixed disulfides, reversed inhibition of p65-NFkappaB DNA binding in extracts from cells treated with hypoxia plus NAC and restored NFkappaB activity. This finding indicated that p65-NFkappaB-SSG was formed in situ under hypoxia plus NAC conditions. In cells, knock-down of endogenous GRx1, which also promotes protein glutathionylation under hypoxic radical generating conditions, prevented NAC-induced NFkappaB inactivation and hypoxic apoptosis. The results indicate that GRx-dependent S-glutathionylation of p65-NFkappaB is most likely responsible for NAC-mediated NFkappaB inactivation and enhanced hypoxic apoptosis. 相似文献
57.
Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor 下载免费PDF全文
Umanskaya K Radke S Chander H Monardo R Xu X Pan ZQ O'Connell MJ Germain D 《Molecular and cellular biology》2007,27(21):7615-7622
Skp2B, an F-box protein of unknown function, is frequently overexpressed in breast cancer. In order to determine the function of Skp2B and whether it has a role in breast cancer, we performed a two-hybrid screen and established transgenic mice expressing Skp2B in the mammary glands. We found that Skp2B interacts with the repressor of estrogen receptor activity (REA) and that overexpression of Skp2B leads to a reduction in REA levels. In the mammary glands of MMTV-Skp2B mice, REA levels are also low. Our results show that in virgin transgenic females, Skp2B induces lobuloalveolar development and differentiation of the mammary glands normally observed during pregnancy. As this phenotype is identical to what was observed for REA heterozygote mice, our observations suggest that the Skp2B-REA interaction is physiologically relevant. However, in contrast to REA(+/-) mice, MMTV-Skp2B mice develop mammary tumors, suggesting that Skp2B affects additional proteins. These results indicate that the observed expression of Skp2B in breast cancer does contribute to tumorigenesis at least in part by modulating the activity of the estrogen receptor. 相似文献
58.
Inhibition of galectin-3 mediated cellular interactions by pectic polysaccharides from dietary sources 总被引:1,自引:0,他引:1
Pectic polysaccharides from dietary sources such as Decalepis hamiltonii—swallow root (SRPP), Hemidesmus indicus (HPP), Nigella sativa—black cumin (BCPP), Andrographis serpyllifolia—(APP), Zingiber officinale—ginger (GRPP) and, citrus pectin (CPP) were examined for galectin inhibitory activity. Inhibition of (a) galectin-3 of MDA-MB-231
cells induced hemagglutination of red blood cells; (b) galectin-3 mediated interaction between normal/metastatic human buccal
cells (NBC)/(MBC) and; (c) invasion of MDA-MB-231 and MBC in the invasive chamber was assessed. Results indicated that SRPP
inhibited hemagglutination at Minimum Inhibitory Concentration (MIC) of 1.86 μg ml−1 equivalent of carbohydrate as apposed to those of BCPP (130 μg ml−1), APP (40 μg ml−1), HPP (40 μg ml−1) and CPP (25 μg ml−1). GRPP even at concentration >1–6 mg ml−1 did not inhibit agglutination. Also SRPP showed ∼15 and 2 fold potent anti hemagglutination activity relative to that of
galectin-3 specific sugars—galactose (MIC-27.1 μg ml−1) and lactose (MIC-4.16 μg ml−1) respectively. Further, SRPP at 10 μg ml−1 inhibited agglutination of NBC by galectin-3 of MDA-MB-231 cells. Modified swallow root pectic polysaccharide (MSRPP) of
50 kDa retained anti hemagglutination activity (MIC of 1.03 μg ml−1) and inhibited MDA-MB-231 and MBC invasion by 73 and 50% with an IC50 of 136 and 200 μg ml−1 respectively. Both SRPP and MSRPP induced apoptosis up to 80% at 100 μg ml−1 concentration by activating ∼2 and 8 folds of Caspase-3 activity. Sugar composition analysis and its correlation with the
galectin inhibitory property indicated that pectic polysaccharides with higher arabinose and galactose content—arabinogalactan
inhibited hemagglutination significantly. 相似文献
59.
Traditional separation techniques do not yield endolysosomes of sufficient purity to permit detailed biochemical characterization of this important class of intracellular vesicles. Here, we have used a magnetic chromatography technique to isolate the endosomes from rat peritoneal macrophages and studied their lipid composition. Electromagnetic isolation works by retention of colloidal iron containing vesicles on magnetic column. The data suggested that both early and late endosomes were rich in cholesterol, whereas sphingomyelin (SM) and specific phospholipids like phosphatidylcholine. phosphatidylethanolamine, phosphatidylglycerol and phosphatidylserine are enriched in the late compartments. Our results also indicated that the purified fractions are enriched in raft lipids like SM, but not in cholesterol. The endosomal purification method described here yields pure endosomes with little or no contamination from mitochondria and hence could be used for further biochemical and marker analysis, giving insight into mechanisms of endocytic traffic. 相似文献
60.
Zhang H Zhi L Moochhala S Moore PK Bhatia M 《American journal of physiology. Lung cellular and molecular physiology》2007,293(4):L960-L971
Increasing data suggest that oxidative stress, due to an increased production of reactive oxygen species and/or a decrease in antioxidants, is involved in the pathophysiology of pulmonary hypertension. Several antioxidant systems regulate the presence of oxidant species in vivo, and of primary interest are the superoxide dismutases (SOD) and catalase. However, little is known about the expression of antioxidant enzymes during the development of pulmonary hypertension. This study uses our lamb model of increased postnatal pulmonary blood flow, secondary to in utero aortopulmonary graft placement (shunt lambs), to investigate the expression patterns as well as activities of antioxidant enzymes during the early development of pulmonary hypertension. Protein levels of catalase, SOD1, SOD2, and SOD3 were evaluated by Western blot, and the activities of catalase and SOD were also quantified. In control lambs, protein expression and activities of catalase and SOD2 increased postnatally (P < 0.05). However, SOD1 and SOD3 protein levels did not change. In shunt lambs, catalase, SOD1, and SOD2 protein levels all increased over the first 8 wk of life (P < 0.05). However, SOD3 did not change. This was associated with an increase in the activities of catalase and SOD2 (P < 0.05). Compared with control lambs, catalase and SOD2 protein levels were decreased in 2-wk-old shunt lambs and this was associated with increased levels of hydrogen peroxide (H(2)O(2)) and superoxide (P < 0.05). Developmentally superoxide but not H(2)O(2) levels significantly increased in both shunt and control lambs with levels being significantly higher in shunt compared with control lambs at 2 and 4 but not 8 wk. These data suggest that the antioxidant enzyme systems are dynamically regulated postnatally, and this regulation is altered during the development of pulmonary hypertension secondary to increased pulmonary blood flow. An increased understanding of these alterations may have important therapeutic implications for the treatment of pulmonary hypertension secondary to increased pulmonary blood flow. 相似文献