共查询到20条相似文献,搜索用时 31 毫秒
1.
Stichopus japonicus Polysaccharide (SJP) is a sulfated polysaccharide from the body wall of the sea cucumber, Stichopus japonicus. Fucoidan is a heparinoid compound that belongs to a family of sulfated polyfucose polysaccharides. Heparin is a glycosaminoglycan. SJP, fucoidan, and heparin profoundly promoted stromal cell-derived factor 1 alpha (SDF-1α)-induced neural stem cell (NSC) migration in a concentration-dependent manner. In addition, the basal migration capacity of cells was significantly promoted after incubation with SJP, fucoidan, or heparin. Interaction of SJP, fucoidan, or heparin with SDF-1α efficiently showed additive effects on the promotion of cell migration from the neurosphere. SJP, fucoidan, or heparin interaction with SDF-1α treatment could increase Nestin expression. SDF-1α modulated by SJP, fucoidan, or heparin activated the CXCR4 receptor and directed cellular migration via the activation of the PI3K/Akt/FOXO3a signaling pathway. Moreover, interaction of SJP, fucoidan, or heparin with SDF-1α effectively promoted NSC migration and induced SDF-1α and CXCR4 expressions. Results suggested that SJP, fucoidan, and heparin might be good candidates for alleviating injury-initiated signals to which NSCs respond. 相似文献
2.
Cross Talk between Adhesion Molecules: Control of N-cadherin
Activity by Intracellular Signals Elicited by
β1 and β3 Integrins in Migrating Neural Crest Cells
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During embryonic development, cell migration and cell differentiation are associated with dynamic modulations both in time and space of the repertoire and function of adhesion receptors, but the nature of the mechanisms responsible for their coordinated occurrence remains to be elucidated. Thus, migrating neural crest cells adhere to fibronectin in an integrin-dependent manner while maintaining reduced N-cadherin–mediated intercellular contacts. In the present study we provide evidence that, in these cells, the control of N-cadherin may rely directly on the activity of integrins involved in the process of cell motion. Prevention of neural crest cell migration using RGD peptides or antibodies to fibronectin and to β1 and β3 integrins caused rapid N-cadherin–mediated cell clustering. Restoration of stable intercellular contacts resulted essentially from the recruitment of an intracellular pool of N-cadherin molecules that accumulated into adherens junctions in tight association with the cytoskeleton and not from the redistribution of a preexisting pool of surface N-cadherin molecules. In addition, agents that cause elevation of intracellular Ca2+ after entry across the plasma membrane were potent inhibitors of cell aggregation and reduced the N-cadherin– mediated junctions in the cells. Finally, elevated serine/ threonine phosphorylation of catenins associated with N-cadherin accompanied the restoration of intercellular contacts. These results indicate that, in migrating neural crest cells, β1 and β3 integrins are at the origin of a cascade of signaling events that involve transmembrane Ca2+ fluxes, followed by activation of phosphatases and kinases, and that ultimately control the surface distribution and activity of N-cadherin. Such a direct coupling between adhesion receptors by means of intracellular signals may be significant for the coordinated interplay between cell–cell and cell–substratum adhesion that occurs during embryonic development, in wound healing, and during tumor invasion and metastasis. 相似文献
3.
Over the past decade, evidence continues to mount showing that N-cadherin is a critical protein in cancer progression and metastasis. In the present study, we evaluated the expression of N-cadherin in human prostate cancer tissue specimens and cell lines. Enhanced expression of N-cadherin was observed in both the malignant and bone-metastasized prostate tissue specimens compared to the healthy prostate tissues. Consistent with the tissue array data, N-cadherin was highly expressed in PC3, but not in Du145 and LNCaP human prostate cell lines. Based on cell to cell binding assay, we found that N-cadherin expression facilitates homotypic interaction between human prostate cancer cells and human microvascular endothelial cells (HMEC). Human angiogenesis antibody array and in vitro angiogenesis assay showed that siRNA-mediated knockdown of N-cadherin reduced the secretion of monocyte chemoattractant protein-1 (MCP-1), which played a potential role in stimulating capillary network formation of HMEC. Additionally, culture supernatant of Du145 cells transfected with full-length N-cadherin expressing plasmid showed increased MCP-1 expression and chemoattractant ability compared to normal Du145 cells. Further, we noticed that blocking PI3K activity inhibited N-cadherin mediated MCP-1 expression. Our data demonstrated that N-cadherin in prostate cancer cell mediates cell–cell adhesion and regulates MCP-1 expression via the PI3K/Akt signaling pathway. 相似文献
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5.
Tong Chen Jin Wang Yuanyuan Li Jianmin Shen Ting Zhao Haixia Zhang 《Glycoconjugate journal》2010,27(6):635-642
A water-soluble polysaccharide (POP1) was isolated from Portulaca oleracea L. Four sulfated derivatives of POP1 (POP1-s1, POP1-s2, POP1-s3 and POP1-s4) were prepared by chlorosulfonic acid method
with N,N-Dicyclohexylcarbodiimide (DCC) as a dehydration-condensation agent. FT-IR spectra and 13C NMR spectra indicated the sulfated groups had been introduced at the C-6 and C-2 positions of POP1. Sulfated derivatives
had different degree of substitution (DS) ranging from 1.01 to 1.81, and different weight-average molecular mass (Mw) ranging
from 41.4 to 48.5 KDa. Sulfated derivatives except POP1-s5 inhibited the growth of HepG2 cells and Hela cells in vitro significantly, which indicated that sulfated modification could enhance cytotoxicity of POP1 on tumor cells. Flow cytometric
studies revealed that sulfated derivatives could mediate the cell-cycle arrest of Hela cells in the S phase. 相似文献
6.
High mobility group box-1 (HMGB1), a potent mediator of inflammation, is known to regulate cellular events through binding
to the multiple cell-surface receptors, including RAGE and TLRs. However, the role of TLR4 and details of HMGB1 signaling
in vascular smooth muscle cells (VSMCs) migration has not been reported so far. The present study was designed to investigate
the hypothesis that HMGB1-induced VSMCs migration is mediated via activation of phosphoinositide 3-kinase/Akt (PI3K/Akt) signalling
pathway through TLR4. VSMCs from rat thoracic aorta were studied. HMGB1 (0.1–1000 ng/ml) stimulated VSMCs migration in a dose-dependent
manner, with the highest value (about 3.5-fold increase). Incubation of VSMCs with 100 ng/ml caused a rapid increase in PI3K
activity and Akt phosphorylation. Migration of VSMCs toward HMGB1 was significantly inhibited by silencing of TLR4 (P < 0.05). We also found pretreated cells with TLR4 siRNA or the PI3 K inhibitor LY294002 could markedly block PI3K/Akt pathway
activation and VSMCs migration mediated by HMGB1 (P both <0.05). In conclusion, HMGB1 induces migration of VSMCs through a TLR4-dependent PI3 K/Akt signaling pathway, which
suggests a possible molecular mechanism for HMGB1 may contribute to neointima formation in restenosis after vascular damage. 相似文献
7.
Phosphoinositide-3 kinase-Rac1-c-Jun NH2-terminal kinase signaling mediates collagen I-induced cell scattering and up-regulation of N-cadherin expression in mouse mammary epithelial cells 总被引:1,自引:0,他引:1
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During epithelial-to-mesenchymal transitions (EMTs), cells must change their interactions with one another and with their extracellular matrix in a synchronized manner. To characterize signaling pathways cells use to coordinate these changes, we used NMuMG mammary epithelial cells. We showed that these cells become fibroblastic and scattered, with increased N-cadherin expression when cultured on collagen I. Rac1 and c-Jun NH2-terminal kinase (JNK) were activated when cells were plated on collagen I, and dominant inhibitory Rac1 (RacN17) or inhibition of JNK signaling prevented collagen I-induced morphological changes and N-cadherin up-regulation. Furthermore, inhibiting phosphoinositide-3 kinase (PI3K) activity prevented Rac1 and JNK activation as well as collagen I-induced N-cadherin up-regulation. These data implicate PI3K-Rac1-JNK signaling in collagen I-induced changes in NMuMG cells. To establish a role for N-cadherin in collagen I-induced cell scattering, we generated N-cadherin overexpressing and knockdown NMuMG cells and showed that knocking down N-cadherin expression prevented collagen I-induced morphological changes. Motility assays showed that cells overexpressing N-cadherin were significantly more motile than mock-transfected cells and that N-cadherin-mediated motility was collagen I dependent. In addition, we showed that cord formation and branching in three-dimensional culture (EMT-dependent events) required N-cadherin expression and PI3K-Rac1-JNK signaling. 相似文献
8.
Antiviral Effects of Sulfated Exopolysaccharide from the Marine Microalga <Emphasis Type="Italic">Gyrodinium impudicum</Emphasis> Strain KG03 总被引:5,自引:0,他引:5
The sulfated exopolysaccharide p-KG03, which is produced by the marine microalga Gyrodinium impudicum strain KG03, exhibited impressive antiviral activity in vitro (EC50 = 26.9 µg/ml) against the encephalomyocarditis virus (EMCV). Depending on the p-KG03 concentration, the development of cytopathic effects in EMCV-infected HeLa cells was either inhibited completely or slowed. Moreover, p-KG03 did not show any cytotoxic effects on HeLa cells, even at concentrations up to 1000 µg/ml. The polysaccharide was purified by repeated precipitation in ethanol, followed by gel filtration. The p-KG03 polysaccharide had a molecular weight of 1.87 × 107, and was characterized as a homopolysaccharide of galactose with uronic acid (2.96% wt/wt) and sulfate groups (10.32% wt/wt). The biological activities of p-KG03 suggest that sulfated metabolites from marine organisms are a rich source of antiviral agents. This is the first reported marine source of antiviral sulfated polysaccharides against EMCV. The p-KG03 polysaccharide may be useful in the development of marine bioactive exopolysaccharide for biotechnological and pharmaceutical products. 相似文献
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10.
Parellel toin vitro differentiation of human monocytes into macrophage-like cells, the cells change their synthesis of glycosaminoglycans from chondroitin 4-sulfate to highly sulfated chondroitin sulfate, containing 4,6-disulfatedN-acetylgalactosamine units [Kolsetet al. (1983) Biochem J 210:661–67]. After exposure of monocyte cultures to [35S]sulfate for 24h either from the onset of cultivation, prior to differentiation, or from day 4, after differentiation,35S-macromolecules from medium and cell-layer were isolated and characterized. The cell-layer of day 5 cultures contained both proteoglycans and free polysaccharide chains, while the35S-macromolecules present in the cell-layer of day 1 cultures and in medium of both monocytes and macrophage-like cells were almost exclusively of proteoglycan nature. Proteoglycans produced by macrophage-like cells were of larger size than the monocyte proteoglycans, most likely due to an increased polysaccharide chain length. These proteoglycans, in contrast to the monocyte-derived species, also showed affinity for fibronectin at physiological ionic strength. 相似文献
11.
The composition, molecular weight and in vitro antioxidant activity of various sulfated polysaccharides obtained by anion
exchange chromatography, acid hydrolysis and radical process degradation of the crude sulfated polysaccharide extracted from
Laminaria japonica were compared. The low sulfated F-A2, with a peak-molecular weight (Mp) of 5–15 kDa, 14.5% sulfated ester and 21.8% glucuronic
acid, exhibited a very strong antioxidant activity on superoxide and hydroxyl radicals, with activity even higher than that
of large molecular weight fractions F-A and F-B. However, highly sulfated fractions with a peak-molecular weight below 15 kDa
had much lower antioxidant activities than other fractions. These results indicated that the sulfate group of the low molecular
weight fractions represents a physical block for the reaction with oxygen radicals. The chemical properties and antioxidant
activities of sulfated polysaccharide fractions obtained by radical process degradation of crude sulfated polysaccharide were
quite different from those obtained by acid hydrolysates. By radical process degradation, the high molecular weight was decreased
to give LM2 (Mp 8 kDa) and LM1 (Mp 1.5 kDa), with a yield of 40% and 15%, respectively. LM2 was enriched with fucose and sulfated
ester, while containing low amounts of glucuronic acid. The antioxidant activity showed that LM2 was unable to scavenge either
superoxide or hydroxyl radical, which suggested that radical process degradation targeted mainly ascopyllan-like species rich
in glucuronic acid, while the fraction rich in sulfated l-fucose remained unchanged. However, LM1 with Mp 1.5 kDa still retained apparent scavenging ability for superoxide radical,
although it contained no glucuronic acid and certain amounts of galactose and mannose as main neutral sugars. These result
suggest that the antioxidant activity of sulfated polysaccharides is apparently related not only to molecular weight and sulfated
ester content, as previously determined, but also to glucuronic acid and fucose content. 相似文献
12.
Antiproliferative activity of sulfated polysaccharide isolated from an enzymatic digest of Ecklonia cava on the U-937 cell line 总被引:1,自引:0,他引:1
Yasantha Athukorala Gin Nae Ahn Young-Heun Jee Gi-Young Kim Soo-Hyun Kim Jin-Hwan Ha Jung-Sook Kang Ki-Wan Lee You-Jin Jeon 《Journal of applied phycology》2009,21(3):307-314
A sulfated polysaccharide purified from a brown alga Ecklonia cava, having high anticoagulant activity was investigated for its antiproliferative effect on murine colon carcinoma (CT-26),
human leukemic monocyte lymphoma (U-937), human promyelocytic leukemia (HL-60), and mouse melanoma (B-16) cell lines. The
sulfated polysaccharide isolated and purified from an enzymatic extract of E. cava had a good selective tumor cell growth inhibition effect; its effect on HL-60 and U-937 was especially promising. The IC50 value for the sulfated polysaccharide from E. cava (ECSP) on U-937 was 43.9 μg mL−1. The presence of the sample in the cell culture media stimulated the induction of apoptosis, revealed by nuclear staining
with Hoechst 33342. The apoptosis induction was confirmed by the cell cycle analysis, while pronounced sub-G1 phase arrests
of 9.5% and 13.8% were also clearly observed when the cells were treated at 15 and 30 μg mL−1 of ECSP in the U-937 cell line, respectively. After a 24-h incubation period, ECSP dose-dependently enhanced the DNA fragmentation
on the U-937 cell line as observed in the agarose gel electrophoresis assay. To rule out the action mechanism of ECSP for
its anticancer activity, some western blot analyses were conducted with several antibodies (caspase-7, caspase-8, Bax, Bcl-xL,
and PARP) and ECSP had a clear effect on the caspase -7 and 8 which cleave protein substrates, including PARP, an inducer
of apoptosis responsible for DNA cleavage. Moreover, ECSP controlled the cellular transmembrane molecules like Bax and Bcl-xL.
Taken together, the above results demonstrate that the apoptosis for antiproliferative effect of ECSP was clearly induced
on U-937 cells. 相似文献
13.
Juan Wang Wenyuan Gao Jian Zhang Tao Huang Tiantian Wen Liming Zhang Luqi Huang 《Plant Growth Regulation》2011,63(3):217-223
In this article, ginsenosides and polysaccharide contents in suspension cells and native roots of Panax quinquefolium L. were studied. In order to enhance the contents of ginsenosides and polysaccharide in P. quinquefolium suspension cells, we tested the effects of lactoalbumin hydrolysate on the growth of P. quinquefolium suspension cell, synthesis of ginsenosides and polysaccharide in flask and bioreactor. In flask culture, cells growth ratio
was significantly enhanced by the addition of lower concentration of lactoalbumin hydrolysate. Addition of 100 mg L−1 lactoalbumin hydrolysate significantly enhanced the contents of total saponins (5.44 mg g−1 DW) and the contents were 3.89-fold over the control group. Addition of lactoalbumin hydrolysate significantly promoted the
accumulation of polysaccharide, except 200 mg L−1 lactoalbumin hydrolysate. The highest total saponins yield (36.72 mg L−1 DW) and polysaccharide yield (0.83 g L−1 DW) were obtained at 100 mg L−1 lactoalbumin hydrolysate. In a 5-L stirred tank bioreactor, the highest contents of total saponins and TRb group ginsenosides
were achieved on day 26, while the effect of lactoalbumin hydrolysate on the contents of TRg group ginsenosides were insignificant.
This result suggests that lactoalbumin hydrolysate might have triggered the enzyme activities for the synthesis of TRb group
ginsenosides. Overall, the highest total saponins yield (31.37 mg L−1 DW) and polysaccharide yield (1.618 g L−1 DW) were obtained on day 26 and day 24 respectively and the polysaccharide yield was 1.95-fold higher than the shake flask
culture (0.83 g L−1 DW). These results provided theoretical reference for two-stage culture in suspension cells of P. quinquefolium in bioreactor. 相似文献
14.
Background
Osteoblasts are bone forming cells that play an essential role in osteogenesis. The elucidation of the mechanisms that control osteoblast number is of major interest for the treatment of skeletal disorders characterized by abnormal bone formation. Canonical Wnt signalling plays an important role in the control of osteoblast proliferation, differentiation and survival. Recent studies indicate that the cell-cell adhesion molecule N-cadherin interacts with the Wnt co-receptors LRP5/6 to regulate osteoblast differentiation and bone accrual. The role of N-cadherin in the control of osteoblast proliferation and survival remains unknown.Methods and Principal Findings
Using murine MC3T3-E1 osteoblastic cells and N-cadherin transgenic mice, we demonstrate that N-cadherin overexpression inhibits cell proliferation in vitro and in vivo. The negative effect of N-cadherin on cell proliferation results from decreased Wnt, ERK and PI3K/Akt signalling and is restored by N-cadherin neutralizing antibody that antagonizes N-cadherin-LRP5 interaction. Inhibition of Wnt signalling using DKK1 or Sfrp1 abolishes the ability of N-cadherin blockade to restore ERK and PI3K signalling and cell proliferation, indicating that the altered cell growth in N-cadherin overexpressing cells is in part secondary to alterations in Wnt signalling. Consistently, we found that N-cadherin overexpression inhibits the expression of Wnt3a ligand and its downstream targets c-myc and cyclin D1, an effect that is partially reversed by N-cadherin blockade. We also show that N-cadherin overexpression decreases osteoblast survival in vitro and in vivo. This negative effect on cell survival results from inhibition of PI3K/Akt signalling and increased Bax/Bcl-2, a mechanism that is rescued by Wnt3a.Conclusion
The data show that N-cadherin negatively controls osteoblast proliferation and survival via inhibition of autocrine/paracrine Wnt3a ligand expression and attenuation of Wnt, ERK and PI3K/Akt signalling, which provides novel mechanisms by which N-cadherin regulates osteoblast number. 相似文献15.
Mona Foth Gennie Parkman Benjamin Battistone Martin McMahon 《Pigment cell & melanoma research》2020,33(5):719-730
Mutational activation of RAC1 is detected in ~7% of cutaneous melanoma, with the most frequent mutation (RAC1C85T) encoding for RAC1P29S. RAC1P29S is a fast‐cycling GTPase that leads to accumulation of RAC1P29S‐GTP, which has potentially pleiotropic regulatory functions in melanoma cell signaling and biology. However, the precise mechanism by which mutationally activated RAC1P29S propagates its pro‐tumorigenic effects remains unclear. RAC1‐GTP is reported to activate the beta isoform of PI3’‐kinase (PIK3CB/PI3Kβ) leading to downstream activation of PI3’‐lipid signaling. Hence, we employed both genetic and isoform‐selective pharmacological inhibitors to test if RAC1P29S propagates its oncogenic signaling in melanoma through PI3Kβ. We observed that RAC1P29S‐expressing melanoma cells were largely insensitive to inhibitors of PI3Kβ. Furthermore, RAC1P29S melanoma cell lines showed variable sensitivity to pan‐class 1 (α/β/γ/δ) PI3’‐kinase inhibitors, suggesting that RAC1‐mutated melanoma cells may not rely on PI3’‐lipid signaling for their proliferation. Lastly, we observed that RAC1P29S‐expressing cell lines also showed variable sensitivity to pharmacological inhibition of the RAC1 → PAK1 signaling pathway, questioning the relevance of inhibitors of this pathway for the treatment of patients with RAC1‐mutated melanoma. 相似文献
16.
Medeiros VP Queiroz KC Cardoso ML Monteiro GR Oliveira FW Chavante SF Guimaraes LA Rocha HA Leite EL 《Biochemistry. Biokhimii?a》2008,73(9):1018-1024
Sulfated polysaccharides (fucans and fucoidans) from brown algae show several biological activities, including anticoagulant
and anti-inflammatory activities. We have extracted a sulfated heterofucan from the brown seaweed Lobophora variegata by proteolytic digestion, followed by acetone fractionation, molecular sieving, and ion-exchange chromatography. Chemical
analyses and 13C-NMR and IR spectroscopy showed that this fucoidan is composed of fucose, galactose, and sulfate at molar ratios of 1:3:2.
We compared the anticoagulant activity of L. variegata fucoidan with those of a commercial sulfated polysaccharide (also named fucoidan) from Fucus vesiculosus and heparin. The experimental inflammation models utilized in this work revealed that fucoidan from L. variegata inhibits leukocyte migration to the inflammation site. Ear swelling caused by croton oil was also inhibited when sulfated
polysaccharides from F. vesiculosus and L. variegata were used. The precise mechanism of different action between homo-and heterofucans is not clear; nevertheless, the polysaccharides
studied here may have therapeutic potential in inflammatory disorders.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 9, pp. 1265–1273. 相似文献
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In this paper, in vitro anti-influenza virus activities of sulfated polysaccharide fractions from Gracilaria lemaneiformis were investigated. Cytotoxicities and antiviral activities of Gracilaria lemaneiformis polysaccharides (PGL), Gracilaria lemaneiformis polysaccharide fraction-1 (GL-1), Gracilaria lemaneiformis polysaccharide fraction-2 (GL-2) and Gracilaria lemaneiformis polysaccharide fraction-3 (GL-3) were studied by the Methyl thiazolyl tetrazolium (MTT) method, and the inhibitory effect
against Human influenza virus H1-364 induced cytopathic effect (CPE) on MDCK cells were observed by the CPE method. In addition,
the antiviral mechanism of PGL was explored by Plaque forming unit (PFU), MTT and CPE methods. The results showed: i) Cytotoxicities
were not significantly revealed, and H1-364 induced CPE was also reduced treated with sulfated polysaccharide fractions from
Gracilaria lemaneiformis; ii) Antiviral activities were associated with the mass percentage content of sulfate groups in polysaccharide fractions,
which was about 13%, in polysaccharides (PGL and GL-2) both of which exhibited higher antiviral activity; iii) A potential
antiviral mechanism to explain these observations is that viral adsorption and replication on host cells were inhibited by
sulfated polysaccharides from Gracilaria lemaneiformis. In conclusion, Anti-influenza virus activities of sulfated polysaccharide fractions from Gracilaria lemaneiformis were revealed, and the antiviral activities were associated with content of sulfate groups in polysaccharide fractions. 相似文献
20.
T. Matsunaga H. Sudo H. Takemasa Y. Wachi N. Nakamura 《Applied microbiology and biotechnology》1996,45(1-2):24-27
The cyanobacterium, Aphanocapsa halo-phytia MN-11, was immobilized in calcium alginate gel and coated on light-diffusing optical fibers (LDOF) for sulfated extracellular
polysaccharide production. Results indicated that sulfated extracellular polysaccharide production depends on the number of
immobilized cells and the light intensity. In addition, the production rate reached 116.0 mg (mg dry cells)-1 day-1 when the cells that were immobilized on LDOF were incubated under a light intensity of 1380 cd sr m-2 at a cell concentration of 1.0×108 cells/cm3 gel. Cells immobilized on LDOF produced about ten times more sulfated extracellular polysaccharide than those immobilized
in calcium alginate beads only (11.7 mg(mg dry cells)-1 day-1).
Received: 31 March 1995/Revised last revision 12 June 1995/Accepted 26 July 1995 相似文献