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At least 217 records · Page 12Linked to original sources
PubMed1998

Chondrocyte-matrix attachment complexes mediate survival and differentiation.

Integrin mediated cell-extracellular matrix interactions are required for survival and differentiation of many cell types. In this review, the cell-matrix attachment complex (CMAX) is described for chondrocytes. The evidence that integrin-mediated signal transduction is necessary for normal chondrocyte differentiation and survival in various culture conditions and in vivo are reviewed. The possible signal transduction pathways stimulated by the extracellular matrix components are discussed with a review of current data from chondrocyte experiments. In addition, the influence of parathyroid hormone and transforming growth factor beta on chondrocyte survival has been included as they may function in concert with integrin mediated signal transduction. Finally, specific changes in gene expression preceding apoptosis are discussed. The current understanding of how integrin-mediated signals prevent apoptosis and implications of anchorage-dependent survival for development and differentiation of the chondrocyte phenotype are discussed.

Animals↗
PubMed2006

Biphosphinic palladacycle complex mediates lysosomal-membrane permeabilization and cell death in K562 leukaemia cells.

The cell death mechanism of cytotoxicity induced by the Biphosphinic Palladacycle Complex (BPC) was studied using a K562 leukaemia cell line. The IC50 values obtained for K562 cells post-72 h of BPC were less than 5.0 microM by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue assays. Using the Acridine Orange vital staining combining fluorescence microscopy it was observed that the complex triggers apoptosis in K562 cells, inducing DNA fragmentation, as analysed through electrophoresis. Lysosomal-membrane permeabilization was also observed in K562 cells post-5 h of BPC, which suggests intralysosomal accumulation by proton-trapping, since its pKa value ranged from 5.1 to 6.5. Caspase-3, and -6 activity induced by BPC in K562 cells was prevented by the cathepsin-B inhibitor [N-(L-3-trans-propylcarbamoyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline] (CA074). These events occurred in the presence of endogenous bcl-2 and bax expression. Acute toxicological studies demonstrated that BPC produces no lesions for liver and kidney fourteen-days after drug administration (100 mg/kg--i.p.). White and red blood cells of BPC-treated mice presented normal morphological characteristics. Taken together, these data suggest a novel lysosomal pathway for BPC-induced apoptosis, in which lysosomes are the primary target and cathepsin B acts as death mediator.

Animals↗
PubMed1993

TRH in dorsal vagal complex mediates acid response to excitation of raphe pallidus neurons in rats.

The role of thyrotropin-releasing hormone (TRH) in the dorsal vagal complex (DVC) in the acid response to excitation of raphe pallidus neurons was investigated in urethan-anesthetized rats with gastric fistula. Kainic acid (0.19 microgram/30 nl) microinjected into the raphe pallidus stimulated gastric acid secretion. The response was prevented by vagotomy. A specific polyclonal TRH antibody, 8964, was raised and characterized (50% inhibitory dose for TRH was 80 pg/ml at an antibody final dilution of 1:10(5)). The TRH antibody injected intracisternally blocked the acid response to intracisternal TRH, but not that of the TRH analogue RX-77368. The TRH antibody (0.33, 0.65, or 1.3 micrograms.100 nl-1.site-1) microinjected bilaterally into the DVC prevented dose dependently by 31, 60, and 76%, respectively, the increase in acid secretion induced by kainic acid injected into the raphe pallidus. The TRH antibody (1.3 microgram/site) microinjected into medullary sites outside of the DVC had no effect. These data indicate that excitation of raphe pallidus neurons induces a vagal-dependent stimulation of gastric acid secretion that is mediated by endogenous TRH in the DVC. TRH neurons in the raphe pallidus projecting to the DVC may have a physiological relevance in the vagal regulation of gastric function.

Animals↗
PubMed1999

The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions.

In the studies reported here, we have examined the properties of the Mcp element from the Drosophila melanogaster bithorax complex (BX-C). We have found that sequences from the Mcp region of BX-C have properties characteristic of Polycomb response elements (PREs), and that they silence adjacent reporters by a mechanism that requires trans-interactions between two copies of the transgene. However, Mcp trans-regulatory interactions have several novel features. In contrast to classical transvection, homolog pairing does not seem to be required. Thus, trans-regulatory interactions can be observed not only between Mcp transgenes inserted at the same site, but also between Mcp transgenes inserted at distant sites on the same chromosomal arm, or even on different arms. Trans-regulation can even be observed between transgenes inserted on different chromosomes. A small 800-bp Mcp sequence is sufficient to mediate these long-distance trans-regulatory interactions. This small fragment has little silencing activity on its own and must be combined with other Polycomb-Group-responsive elements to function as a "pairing-sensitive" silencer. Finally, this pairing element can also mediate long-distance interactions between enhancers and promoters, activating mini-white expression.

Animals↗
PubMed1997

Prostaglandins and nitric oxide in copper-complex mediated protection against ethanol-induced gastric damage.

This study was designed to determine the effects of oral administration of the copper(II) complex of amino acids, on gastric lesions induced by ethanol in rats and the possible mechanism(s) of protection. The copper(II) complex of L-tryptophan and L-phenylalanine is reported as the most effective in reducing ulcer numbers as well as ulcer severity of the many amino acid complexes studied. We investigated the role of PGE2 and nitric oxide (NO) in the protection afforded by Cu(II)(L-Trp)(L-Phe) against ethanol-induced damage. The involvement of endogenous eicosanoids and NO was evaluated with the respective inhibitors of prostaglandin and NO synthesis, indomethacin and NG-nitro-L-arginine (L-NNA). Ex vivo PGE2 accumulation in the rat gastric mucosa has also been determined. Pretreatment with indomethacin only partially counteracted the protective activity of Cu(II)(L-Trp)(L-Phe). L-NNA did not attenuate the protection by Cu(II)(L-Trp)(L-Phe), which was reduced but not prevented by indomethacin, suggesting that prostanoids contribute to the Cu(II)(L-Trp)(L-Phe) protective effect, together with some mechanism(s) other than NO synthesis.

Animals↗
PubMed1999

B cell responses to a peptide epitope. VIII. Immune complex-mediated regulation of memory B cell generation within germinal centers.

Using an in vivo reconstitution assay, we examine here the role of immune complexes in both formation of germinal centers (GC) and processes that occur subsequently within. The presence of Ag, as immune complexes, was found not to constitute a limiting requirement for the initiation of GC formation. No detrimental effect either on numbers or sizes of the resulting GC was observed when Ag-containing immune complexes were omitted during reconstitution. Thus, both recruitment and proliferation of Ag-activated B cells within GC appear not to be limited by Ag concentrations. In contrast, the presence of immune complexes was observed to be obligatory for the generation of Ag-specific memory B cells. This optimally required immune complexes to be constituted by IgG-class Abs with epitope specificities that were homologous to those of the GC B cells. The GC reaction was also found to be characterized by an enhancement of Ab specificity for the homologous epitope. Although some improvement in specificity was noted in recall responses from immune complex-deficient GC, the presence of appropriate immune complexes served to further optimize the outcome. Here again, isotype and epitope-specificity of the Ab constituent in immune complexes proved to be important.

Amino Acid Sequence↗
PubMed2006

Formation of linear polymers with pendant vinyl groups via inclusion complex mediated polymerization of divinyl monomers.

Ethylene glycol dimethacrylate (EGDMA) and ethylene glycol methacrylate 4-vinyl benzoate (EGMAVB) were shown to form 1:1 inclusion complexes with cyclodextrin and were characterized by instrumental techniques. Computational analysis showed that the bent conformation of the included divinyl monomer was more stable than its linear conformation. Complexation of the divinyl monomer with the first CD molecule offered substantial stabilization than with the second CD molecule. The vinyl group included in the CD cavity did not participate in polymerization. As a result, solvent soluble, linear polymers with pendant vinyl unsaturation per repeat unit were obtained. This was unequivocally established by the polymerization of a complex comprising CD and EGMAVB. The unreacted vinyl group can be polymerized in the subsequent step to yield cross-linked products.

Biocompatible Materials↗
PubMed2004

Positive and negative functions of the SAGA complex mediated through interaction of Spt8 with TBP and the N-terminal domain of TFIIA.

A surface that is required for rapid formation of preinitiation complexes (PICs) was identified on the N-terminal domain (NTD) of the RNA Pol II general transcription factor TFIIA. Site-specific photocross-linkers and tethered protein cleavage reagents positioned on the NTD of TFIIA and assembled in PICs identified the SAGA subunit Spt8 and the TFIID subunit Taf4 as located near this surface. In agreement with these findings, mutations in Spt8 and the TFIIA NTD interact genetically. Using purified proteins, it was found that TFIIA and Spt8 do not stably bind to each other, but rather both compete for binding to TBP. Consistent with this competition, Spt8 inhibits the binding of SAGA to PICs in the absence of activator. In the presence of activator, Spt8 enhances transcription in vitro, and the positive function of the TFIIA NTD is largely mediated through Spt8. Our results suggest a mechanism for the previously observed positive and negative effects of Spt8 on transcription observed in vivo.

Amino Acid Sequence↗
PubMed2004

Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis.

Deposition of the major histone H3 (H3.1) is coupled to DNA synthesis during DNA replication and possibly DNA repair, whereas histone variant H3.3 serves as the replacement variant for the DNA-synthesis-independent deposition pathway. To address how histones H3.1 and H3.3 are deposited into chromatin through distinct pathways, we have purified deposition machineries for these histones. The H3.1 and H3.3 complexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DNA-synthesis-dependent and -independent nucleosome assembly, respectively. Notably, these complexes possess one molecule each of H3.1/H3.3 and H4, suggesting that histones H3 and H4 exist as dimeric units that are important intermediates in nucleosome formation. This finding provides new insights into possible mechanisms for maintenance of epigenetic information after chromatin duplication.

Cell Cycle Proteins↗
PubMed1980

Immune complex-mediated rheumatic diseases: the evidence and the enigmas.

Clearly, many of the connective tissue disorders are intimately associated with either focal tissue evidence of immune complex deposition or markedly elevated levels of complexes during acute disease activity. In many diseases, such as systemic lupus erythematosus or rheumatoid arthritis, the immune complexes have been firmly established as basic elements in pathogenesis. In other disorders, however, the presence or measurable elevation of circulating immune complex materials may represent an epiphenomenon that reflects tissue injury secondary to the underlying inflammatory process. Much more precise definition of these problems awaits further longitudinal study.

Antibodies, Antinuclear↗
PubMed2004

Habitat structural complexity mediates the foraging success of multiple predator species.

We investigated the role of freshwater macrophytes as refuge by testing the hypothesis that predators capture fewer prey in more dense and structurally complex habitats. We also tested the hypothesis that habitat structure not only affects the prey-capture success of a single predator in isolation, but also the effectiveness of two predators combined, particularly if it mediates interactions between the predators. We conducted a fully crossed four-factorial laboratory experiment using artificial plants to determine the separate quantitative (density) and qualitative (shape) components of macrophyte structure on the prey-capture success of a predatory damselfly, Ischnura heterosticta tasmanica, and the southern pygmy perch, Nannoperca australis. Contrary to our expectations, macrophyte density had no effect on the prey-capture success of either predator, but both predators were significantly less effective in the structurally complex Myriophyllum analogue than in the structurally simpler Triglochin and Eleocharis analogues. Furthermore, the greater structural complexity of Myriophyllum amplified the impact of the negative interaction between the predators on prey numbers; the habitat use by damselfly larvae in response to the presence of southern pygmy perch meant they captured less prey in Myriophyllum. These results demonstrate habitat structure can influence multiple predator effects, and support the mechanism of increased prey refuge in more structurally complex macrophytes.

Analysis of Variance↗
PubMed1981

Lymphocytotoxic activity in primary glomerulonephritis: evidence for immune complex-mediated cytotoxicity.

Sera from 84 patients with primary glomerulonephritis (GN) were tested for lymphocytotoxic activity (LCA) against panels of (a) normal peripheral lymphocytes and (b) B-lymphocytes obtained from patients with chronic lymphatic leukaemia (CLL). Significant LCA was found particularly in minimal change GN, acute post-streptococcal GN (AGN-PS) and mesangiocapillary GN (MCGN) where 62%, 75% and 45% respectively of samples were positive. No correlation was observed between LCA and levels of C3 or immune complexes. All but three positive sera showed reactivity against T and B cells; these three showed only T cell cytotoxicity. Fractionation of 6 sera (2 minimal change GN; 2 AGN-PS; 2 MCGN) on Sephadex G200 showed cell killing to reside in the exclusion peak. When samples were separated under dissociating conditions at pH 3.0, there was significant reduction in LCA (P less than 0.001) compared to that of fractions collected at pH 7.2. The same protocol did not affect the lymphocytotoxicity of anti-human lymphocyte globulin. The data suggest that lymphocyte killing in GN is mediated at least in part by antigen/antibody complex activity. The reaction is immunochemically similar to that seen in systemic lupus erythematosus and may have comparable implications for antibody regulation in GN.

Antigen-Antibody Complex↗
PubMed1995

A cap-binding protein complex mediating U snRNA export.

Cap structures are added cotranscriptionally to all RNA polymerase II transcripts. They affect several processes including RNA stability, pre-messenger RNA splicing, RNA export from the nucleus and translation initiation. The effect of the cap on translation is mediated by the initiation factor eIF-4F, whereas the effect on pre-mRNA splicing involves a nuclear complex (CBC) composed of two cap binding proteins, CBP80 and CBP20. A role for CBC in the nuclear export of capped RNAs has also been proposed. We report here the characterization of human and Xenopus CBP20s. Antibodies against recombinant CBP20 prevent interaction of CBC with capped RNAs in vitro. Following microinjection into Xenopus oocytes, the antibodies inhibit both pre-mRNA splicing and export of U small nuclear RNAs to the cytoplasm. These results demonstrate that CBC mediates the effect of the cap structure in U snRNA export, and provide direct evidence for the involvement of a cellular RNA-binding factor in the transport of RNA to the cytoplasm.

Amino Acid Sequence↗
PubMed1995

Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CD14.

Endotoxin (lipopolysaccharide; LPS) activates a wide variety of host defense mechanisms. In mammals LPS binding protein (LBP) and CD14 interact with LPS to mediate cellular activation. Using sucrose density gradients and a fluorescent endotoxin derivative we have investigated the mechanism of LPS binding to LBP and the soluble form of CD14 (sCD14). LPS binds to LBP to form two types of complex; at low ratios of LPS to LBP complexes with one molecule of LBP and 1-2 molecules of LPS predominate, while at high ratios of LPS to LBP a large aggregate of LBP and LPS predominates. Complexes of LPS with sCD14 do not form large aggregates, consisting of only 1-2 LPS bound to a single sCD14 even at high multiples of LPS to sCD14. LBP catalyzes LPS binding to sCD14. Catalysis by LBP apparently occurs because LBP provides a pathway for LPS to bind to sCD14 which avoids the necessity for LPS monomers in aqueous solution. The dissociation constants for LPS.LBP and LPS.sCD14 complexes were determined to be 3.5 x 10(-9) and 29 x 10(-9) M, respectively. These numbers suggest that when LBP and sCD14 are present at roughly equal concentrations as they are in normal human plasma and compete for limited LPS, the LPS will predominantly associate with LBP.

Acute-Phase Proteins↗
PubMed1997

Spc98p and Spc97p of the yeast gamma-tubulin complex mediate binding to the spindle pole body via their interaction with Spc110p.

Previously, we have shown that the yeast gamma-tubulin, Tub4p, forms a 6S complex with the spindle pole body components Spc98p and Spc97p. In this paper we report the purification of the Tub4p complex. It contained one molecule of Spc98p and Spc97p, and two or more molecules of Tub4p, but no other protein. We addressed how the Tub4p complex binds to the yeast microtubule organizing center, the spindle pole body (SPB). Genetic and biochemical data indicate that Spc98p and Spc97p of the Tub4p complex bind to the N-terminal domain of the SPB component Spc110p. Finally, we isolated a complex containing Spc110p, Spc42p, calmodulin and a 35 kDa protein, suggesting that these four proteins interact in the SPB. We discuss in a model, how the N-terminus of Spc110p anchors the Tub4p complex to the SPB and how Spc110p itself is embedded in the SPB.

Calmodulin-Binding Proteins↗
PubMed1994

Cooperativity between two NF-kappa B complexes, mediated by high-mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter.

Cytokine-induced expression of the E-selectin gene requires the promoter binding and interaction of the transcription factors NF-kappa B and ATF. Here we have further analyzed the E-selectin promoter and revealed an additional region (nucleotides -140 to -105 [-140/-105]) which is essential in controlling promoter activation by cytokines. We identified high-mobility-group protein I(Y) [HMG-I(Y)] interacting specifically at two sites within this region. We noted that one of the HMG-I(Y)-binding sites overlaps a sequence element (-127/-118) diverging at only one position from the NF-kappa B consensus binding sequence. This led us to ask whether the -127/-118 element represents a second functional NF-kappa B-binding site within the E-selectin promoter. Using specific antisera, we show that p50, p65, and, interestingly, RelB are components of the complex interacting at this site. Mutational analysis of the -127/-118 NF-kappa B site indicates that both NF-kappa B and HMG-I(Y) binding at this site are essential for interleukin-1 induction of the promoter. We demonstrate that the binding affinity of the p50 subunit of NF-kappa B to both NF-kappa B sites within the E-selectin promoter is significantly enhanced by HMG-I(Y). In addition, an essential role for cooperative interaction between the two NF-kappa B complexes is shown by the requirement for both NF-kappa B sites to mediate E-selectin promoter activation by interleukin-1 and p50/p65 expression. We conclude that HMG-I(Y) mediates binding of a distinct NF-kappa B complex at two sites within the E-selectin promoter. Furthermore, a unique cooperativity between these NF-kappa B complexes is essential for induced E-selectin expression. These results suggest mechanisms by which NF-kappa B complexes are involved in specific gene activation.

Base Sequence↗