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At least 271 records · Page 15Linked to original sources

PubMed2006

Anti-CD45 antibody enhances lipoxygenase pathway of human naïve mononuclear cells and cyclooxygenase pathway of neutrophils.

OBJECTIVE AND DESIGN: Anti-CD45 antibody exhibits multiple biological effects on human mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN). We intended to determine whether anti-CD45 antibody could affect arachidonic acid metabolism and thereby, the interactions between human naïve MNC and PMN. MATERIALS AND METHODS: Human naïve MNC and PMN were incubated with monoclonal anti-human CD45 IgG F(ab')(2) antibody or non-specific IgG F(ab')(2) for 30 min. The mRNA expression of cyclooxygenase type 1 (COX-1), type 2 (COX-2), 5-lipoxygenase (5-LOX) and leukotriene A(4) hydrolase (LTA(4) hydrolase) in both cells was detected by RT-PCR and quantified by densitometric determination. The presence of COX-1 and COX-2 molecules in the cells was detected by Western blot. The concentration of PGE(2) and LTB(4) in cultured supernatants was measured by EIA kits. RESULTS: Anti-CD45 IgG F(ab')(2) up-regulated LTA(4) hydrolase mRNA expression and LTB(4) production, but down-regulated COX-1 and COX-2 mRNA expression and PGE2 production, of naïve MNC compared to non-specific IgG F(ab')(2). In contrast, a reverse modulation by the specific antibody on PMN was observed including up-regulation of cyclooxygenase pathway and down-regulation of lipoxygenase pathway. CONCLUSIONS: A novel activity of anti-CD45 with reverse modulation on cyclooxygenase/lipoxygenase pathways was found such that the expression of COX-1 and COX-2 in PMN, and 5-LOX and LTA(4) hydrolase in MNC were enhanced.

Antibodies↗

PubMed2003

Expression of a hypovirulence-causing double-stranded RNA is associated with up-regulation of quinic acid pathway and down-regulation of shikimic acid pathway in Rhizoctonia solani.

We reported previously that a 3.6-kb double-stranded RNA, designated as M2, is associated with hypovirulence in the Rhizoctonia solani isolate Rhs 1A1 and proposed that the M2-encoded putative polypeptide A (pA) might interfere with the regulation of the quinate and shikimate pathways. In this study, Western blot analysis showed that a protein band of the predicted size (83 kDa) binds antibodies specific to a pA epitope and is detectable in M2-containing but not in M2-lacking cultures. A mRNA, associated with Rhs 1A1 polysomes immunoprecipitated with anti-pA antibodies, has a sequence basically identical to that of the sense-strand of M2. The normally inducible quinate pathway was constitutively expressed, whereas the shikimate pathway was down-regulated in the M2-containing, hypovirulent Rhs 1A1. Finally, the relative concentration of phenylalanine, precursor of the virulence determinant phenylacetic acid, was correlated with the degree of pathogenicity in the virulent Rhs 1AP but not in the hypovirulent Rhs 1A1.

Gene Expression Regulation, Fungal↗

PubMed2003

A genomewide survey of developmentally relevant genes in Ciona intestinalis. V. Genes for receptor tyrosine kinase pathway and Notch signaling pathway.

In the present survey, we identified most of the genes involved in the receptor tyrosine kinase (RTK), mitogen activated protein kinase (MAPK) and Notch signaling pathways in the draft genome sequence of Ciona intestinalis, a basal chordate. Compared to vertebrates, most of the genes found in the Ciona genome had fewer paralogues, although several genes including ephrin, Eph and fringe appeared to have multiplied or duplicated independently in the ascidian genome. In contrast, some genes including kit/flt, PDGF and Trk receptor tyrosine kinases were not found in the present survey, suggesting that these genes are innovations in the vertebrate lineage or lost in the ascidian lineage. The gene set identified in the present analysis provides an insight into genes for the RTK, MAPK and Notch signaling pathways in the ancient chordate genome and thereby how chordates evolved these signaling pathway.

Animals↗

PubMed2006

Tacrolimus and cyclosporine A inhibit human osteoclast formation via targeting the calcineurin-dependent NFAT pathway and an activation pathway for c-Jun or MITF in rheumatoid arthritis.

In the present study, we aimed to determine whether tacrolimus (FK506) and cyclosporine A act directly on human osteoclast precursors obtained from patients with rheumatoid arthritis (RA) and influence monocyte-osteoclast differentiation induced by receptor activator of NF-kappaB ligand (RANKL) in vitro, the stage at which differentiation was affected and the manner in which tacrolimus or cyclosporine A affected the osteoclast signaling pathway. Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and cultured in the presence of RANKL and macrophage-colony stimulating factor (M-CSF). Tacrolimus or cyclosporine A was added to these cultures to determine the effect on the osteoclast differentiation. Osteoclast formation was determined by assessing the number of tartrate resistant acid phosphatase (TRAP) staining cells and measuring the extent of lacunar resorption. The expression of osteoclast transcription factors, such as TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells c1 (NFATc1), c-Fos, c-Jun, microphthalmia transcription factor (MITF) and PU.1 in mononuclear cells (MNCs) was assayed by quantitative reverse transcription-polymerase chain reaction. Addition of tacrolimus or cyclosporine A resulted in a decrease in the number of TRAP-positive multinucleated cells (TRAP+ MNCs) and a decrease in the extent of lacunar resorption pit formation as compared to the control cultures; thus, human monocyte-osteoclast differentiation was more effectively inhibited at the late stage and addition of tacrolimus or cyclosporine A resulted in a decrease in the mRNA expression of NFATc1, c-Jun, and MITF at the late stage. Our results suggest that tacrolimus or cyclosporine A acts directly on human osteoclast precursors in RA patients and exerts their immunosuppressive effects on human monocyte-osteoclast formation via targeting both the calcineurin-dependent NFAT pathway and activation pathway for c-Jun or MITF.

Adolescent↗

PubMed2006

Ablation of difficult right-sided accessory pathways aided by mapping of tricuspid annular activation using a Halo catheter : Halo-mapping of right sided accessory pathways.

OBJECTIVE: To demonstrate that the use of a 20-pole catheter (Halotrade mark) positioned around the tricuspid valve annulus (TVA) is helpful in rapidly localising right free wall accessory pathways (AP), enhancing catheter stability during ablation, and leading to increased success in ablating these challenging pathways. PATIENTS AND METHODS: Seven consecutive patients who underwent Halo-mapping of right-sided AP were studied. All but one had previously failed ablation. With a Halo catheter deployed at TVA, the accessory pathway location was rapidly identified using the sites of earliest atrial (A) activation during ventricular (V) pacing or orthodromic tachycardia, or earliest V-activation during sinus rhythm or A-pacing were identified. The stability of the ablation catheter was guided fluoroscopically (with reference to the stationary Halo), and electrically (contact artefact between the ablation catheter and Halo poles). RESULTS: AP locations were identified by the Halo (anterior in one patient, antero-lateral in one, lateral in two, and postero-lateral in three) where similar local VA/AV intervals were recorded at both the ablation catheter and Halo bipoles recording the shortest VA/AV intervals (four of seven patients), contact artefact between the ablation catheter and those Halo bipoles was seen (six of seven patients), or both (three of seven patients). All APs were ablated successfully after a mean RF duration of 5+/-2 min, and 25+/-17 min post Halo deployment without clinical recurrence at 12+/-4 months follow-up. CONCLUSION: A Halo positioned at the TVA can ease the localisation of right-sided AP, facilitate catheter stability during ablation, and guides successful ablation.

Adult↗

PubMed1982

Regulation of pathways of glucose metabolism in kidney. Specific linking of pentose phosphate pathway activity with kidney growth in experimental diabetes and unilateral nephrectomy.

The pentose phosphate pathway operates at an elevated level in rat kidney following induction of diabetes and in the compensatory hypertrophy following unilateral nephrectomy in control and alloxan-diabetic rats, as shown by the yields of 14CO2 from [1-14C]glucose, [6-14C]glucose and 3H2O yields from [2-3H]glucose. The elevated flux through the pentose phosphate pathway is correlated with the increased RNA content and weight of the kidney. The direct utilization of NADPH for reductive synthetic reactions and the potential for indirect utilization via the sorbitol route and the linked transhydrogenase reactions of the glucuronate-xylulose pathway, for NADH and ATP generation, are also discussed.

Animals↗

PubMed1991

The recA-recBCD dependent recombination pathways of Serratia marcescens and Proteus mirabilis in Escherichia coli: functions of hybrid enzymes and hybrid pathways.

The physical maps of cloned recBCD gene regions of Serratia marcescens and Proteus mirabilis were correlated to genes located in this region. The genes thyA, recC, recB, recD and argA were organized as in Escherichia coli. The 3 rec genes code for the 3 different subunits of the RecBCD enzyme and produced enzymes promoting recombination and repair of UV damage in E coli. The recBCD-dependent stimulation of recombination at specific nucleotide sequences called Chi (Chi-activation) was determined in lambda red-gam-crosses. Chi-activation by the different RecBCD enzymes decreased in the order E coli greater than S marcescens greater than P mirabilis. In E coli cloned subunits genes from S marcescens and P mirabilis led to the formation of functional hybrid enzymes consisting of subunits from 2 or even 3 species. The origin of the RecC subunit present in the hybrid enzymes affected the degree of Chi-activation. Further, changes in Chi-activation occurred when the RecD subunit in the enzyme from E coli was replaced by RecD proteins from S marcescens or P mirabilis. This suggested that the RecD subunit determines not only whether or not Chi-activation is possible but also to which extent it occurs. Finally we have reconstituted recombination pathways of S marcescens and P mirabilis by combining the cloned recA and recBCD genes from these species in E coli deleted for recA and recBCD. Both pathways can efficiently promote recombination and repair. Studies are summarized which showed that levels of repair and recombination promoted by the recA-recBCD genes are mostly higher when the recA and recBCD genes came from the same species than from 2 different species (hybrid RecBCD recombination pathway). The data are interpreted to provide evidence that in vivo the RecA protein co-operates with the RecBCD enzyme in recombination and repair of UV damage.

Chromosome Mapping↗

PubMed2006

EGFR signaling pathway negatively regulates PSA expression and secretion via the PI3K-Akt pathway in LNCaP prostate cancer cells.

Epidermal growth factor (EGF) and its receptor (EGFR) are involved in hormone-refractory growth and poor prognosis of a subgroup of human prostate cancer. In this communication, we investigated the regulation of PSA by the EGFR signaling pathway using LNCaP C-81 prostate cancer cells. Administration of EGF stimulated the growth of LNCaP C-81 cells, however, PSA expression and secretion were suppressed. An EGFR inhibitor, AG1478, abrogated the PSA suppression effect by EGF, in concurrence with the suppression of tyro-phosphorylation levels of EGFR. Interestingly, the AR level was also decreased in EGF-treated LNCaP C-81 cells. Moreover, LY294002, but not PD98059, inhibited the PSA and AR suppression effect by EGF in concurrence with the suppression of phosphorylation levels of Akt. In conclusion, our results strongly suggest the existence of a novel androgen-independent PSA regulatory mechanism, i.e., the EGFR signaling pathway negatively regulates PSA expression which may be induced by the alteration of AR expression via the PI3K-Akt pathway in LNCaP C-81 cells.

Androgens↗

PubMed2005

Prediction of regulatory pathways using mRNA expression and protein interaction data: application to identification of galactose regulatory pathway.

We propose a novel technique that constructs gene regulatory networks from DNA microarray data and gene-protein databases and then applies Mason rule to systematically search for the most dominant regulators of the network. The algorithm then recommends the identified dominant regulator genes as the best candidates for future knock-out experiments. Actively choosing the genes for knock-out experiments allows optimal perturbation of the pathway and therefore produces the most informative DNA microarray data for pathway identification purposes. This approach is more practically advantageous in analysis of large pathways where the time and cost of DNA microarray data experiments can be reduced using the proposed optimal experiment design. The proposed method was successfully tested on the galactose regulatory network.

Animals↗

PubMed2006

Role of the peripheral heme oxygenase-carbon monoxide pathway on the nociceptive response of rats to the formalin test: evidence for a cGMP signaling pathway.

The aim of the present study was to investigate the role of the peripheral heme oxygenase (HO)-carbon monoxide (CO) pathway on nociceptive response of rats to the formalin experimental model of pain. Animals were handled and adapted to the experimental environment for a few days before the formalin test was applied. For the formalin test, 50 microl of a 1% formalin solution was used and injected subcutaneously in the dorsal surface of the right hind paw. Following injections, animals were observed for 1 h, and flinching behavior was measured as the nociceptive response. Twenty minutes before the test rats were pretreated with podal injections with the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is known to induce the HO pathway. Control animals were treated with vehicles. We observed a significant increase on nociceptive response of rats treated with ZnDPBG, and a drastic reduction of flinching nociceptive behavioral response in the heme-lysinate and CO treated animals. Among the three different HO products, CO seems to account for the heme-lysinate effect because the injection of the gas attenuated the flinching response whereas biliverdine and deferoxanine (an iron chelator) failed to cause any significant change. Furthermore, CO seems to act via cGMP, since methylene blue (a soluble guanylate cyclase inhibitor) prevented the reduction of the flinching nociceptive behavioral response caused by heme-lysinate. These findings strongly indicate that CO is the HO pathway product that plays an antinociceptive role during the formalin test, acting via cGMP.

Animals↗

PubMed2005

A novel functional activator of the Drosophila JAK/STAT pathway, unpaired2, is revealed by an in vivo reporter of pathway activation.

Striking similarities continue to emerge between the mammalian and Drosophila JAK/STAT signaling pathway. However, until now there has not been the ability to monitor global pathway activity during development. We have generated a transgenic animal with a JAK/STAT responsive reporter gene that can be used to monitor pathway activation in whole Drosophila embryos. Expression of the lacZ reporter regulated by STAT92E binding sites can be detected throughout embryogenesis, and is responsive to the Janus Kinase hopscotch and the ligand upd. The system has enabled us to identify the effect of a predicted gene related to upd, designated upd2, whose expression initiates during germ band extension. The stimulatory effect of upd2 on the JAK/STAT reporter can also be demonstrated in Drosophila tissue culture cells. This reporter system will benefit future investigations of JAK/STAT signaling modulators both in whole animals and tissue culture.

Amino Acid Sequence↗

PubMed2005

Sources and pathways of selected organochlorine pesticides to the Arctic and the effect of pathway divergence on HCH trends in biota: a review.

Historical global usage and emissions for organochlorine pesticides (OCPs), including hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethane (DDT), toxaphene and endosulfan, are presented. Relationships between the air concentrations of these OCPs and their global emissions are also discussed. Differences between the pathways of alpha- and beta-HCH to the Arctic Ocean are described in the context of environmental concentrating and diluting processes. These concentrating and diluting processes are shown to control the temporal and spatial loading of northern oceans and that the HCH burdens in marine biota from these oceans respond accordingly. The HCHs provide an elegant example of how hemispheric-scale solvent switching processes can alter the ocean into which an HCH congener partitions, how air-water partitioning controls the pathway for HCHs entering the Arctic, and how the various pathways impact spatial and temporal trends of HCH residues in arctic animals feeding out of marine and terrestrial foodwebs.

Animals↗

PubMed1997

The ATP-induced K(+)-transport pathway of yeast mitochondria may function as an uncoupling pathway.

The effect of the presence of K+ during oxidative phosphorylation measured on isolated yeast mitochondria was dependent on phosphate concentration. At 0.5 mM phosphate, K+ did promote an uncoupling of oxidative phosphorylation, which was prevented by decavanadate, a potent inhibitor of the ATP-induced K(+)-transport pathway. AT 5 mM phosphate, no uncoupling effect of K+ could be evidenced. These data suggest that the ATP-induced K(+)-transport pathway may, under certain conditions, function as an uncoupling pathway of oxidative phosphorylation.

Adenosine Triphosphate↗

PubMed2002

Incorporation of lipophilic pathways into the porous pathway model for describing skin permeabilization during low-frequency sonophoresis.

Application of low-frequency sonophoresis (LFS) has been shown to increase skin permeability, thereby facilitating delivery of hydrophilic solutes. We have previously shown that the modified porous pathway model provides an adequate theoretical description of transdermal delivery of hydrophilic solutes through pores in the presence and absence of ultrasound. However, small hydrophilic solutes (M(w)<400 Da) that exhibit a moderate partition coefficient, K(o/w) (0.1<K(o/w)<1), may also have a substantial contribution to permeability from transport through intercellular lipid bilayers. The aim of this note is to incorporate the lipophilic pathway into the porous pathway model to describe transdermal drug transport in the absence and presence of ultrasound.

Membrane Lipids↗

PubMed1999

Creation of transdermal pathways for macromolecule transport by skin electroporation and a low toxicity, pathway-enlarging molecule.

A combined electrical (HV, "high voltage", pulsing) and chemical (topical sodium thiosulfate) intervention is hypothesized to create enlarged aqueous pathways that allow large quantities of macromolecules to be transported through human skin's stratum corneum (SC), the dominant barrier for transdermal drug delivery and biochemical analyte extraction. This expectation is based on the known structure and composition of the SC, and previous models and experiments for local transport regions (LTRs) due to transdermal HV pulsing. In vitro experiments demonstrated that transdermal macromolecule fluxes of 10(-9) to 10(-8) mol h(-1) cm(-2) (10 to 100 microg h(-1) cm(-2)) or greater are possible for lactalbumin and an antibody (IgG), which are potentially therapeutic values for peptides, proteins and nucleic acids. In the absence of sodium thiosulfate, only a small molecule (sulforhodamine) flux increased significantly, consistent with many previous studies. Significant macromolecule transdermal fluxes occurred only if a pathway enlarging molecule (sodium thiosulfate) was present. Our results also provide support for the mechanism hypothesis that HV pulses leading to transdermal voltages U(skin) > 50 V create straight-through aqueous pathways that penetrate multilamellar bilayer membranes, corneocyte envelopes and corneocyte interiors within the SC.

Electroporation↗

PubMed2003

A method for classifying metabolites in topological pathway analyses based on minimization of pathway number.

Metabolic pathway analysis based on the concept of elementary flux mode is a valuable tool for reconstruction of bacterial metabolisms and in predicting optimal conversion yields in biotechnology. However, pathway analysis of large and highly entangled metabolic networks meets the problem of combinatorial explosion of possible routes across the networks. Here we propose a method for coping with this problem by suitably classifying metabolites as external or internal. External metabolites are considered to have buffered concentrations while internal metabolites have to fulfil a balance condition at steady state. For many substances such as nutrients and excreted products, there are biochemical reasons to classify them as external. In addition, other substances (especially at central branching points) can operationally be considered external in order to avoid combinatorial explosion. We suggest to find such a classification of metabolites that minimizes the number of elementary flux modes (pathways). This is motivated by the objectives of finding such a description of the system that reduces as much as possible the amount of necessary data and of removing the ambiguity and arbitrariness in the classification of metabolites in an automated, systematic way. For networks of moderate size, the solution to this combinatorial minimization problem can be found by exhaustive search. To tackle also larger systems, a stochastic optimization program based on the Metropolis algorithm was developed. Both methods are applied, for illustration, to several reaction schemes including a larger network representing glutathione metabolism.

Combinatorial Chemistry Techniques↗

PubMed1996

On-pathway versus off-pathway folding intermediates.

Rapidly formed molten globule intermediates accumulate at the start of the folding reactions of several small proteins. Opinion is sharply divided as to whether they are on-pathway or off-pathway intermediates. I discuss recent experiments aimed at resolving this issue. Specific points include whether a 'rollover' in the plot of folding rate versus denaturant concentration implies that a folding intermediate is or is not on-pathway; whether the failure to observe folding intermediates for some small proteins implies a different folding mechanism or only that the intermediates are less stable; possible interpretation of 'fast-track' folding of hen lysozyme; and the significance of recent results in the search for unfolding intermediates.

Animals↗

PubMed2002

Pathway of oxidative folding of alpha-lactalbumin: a model for illustrating the diversity of disulfide folding pathways.

The pathway of oxidative folding of alpha-lactalbumin (alpha LA) (four disulfide bonds) has been characterized by structural and kinetic analysis of the acid-trapped folding intermediates. In the absence of calcium, oxidative folding of alpha LA proceeds through highly heterogeneous species of one-, two-, three-, and four-disulfide (scrambled) intermediates to reach the native structure. In the presence of calcium, the folding intermediates of alpha LA comprise two predominant isomers (alpha LA-IIA and alpha LA-IIIA) adopting exclusively native disulfide bonds, including the two disulfide bonds (Cys(61)-Cys(77) and Cys(73)-Cys(91)) located within the beta-sheet calcium binding domain. alpha LA-IIA is a two-disulfide species consisting of Cys(61)-Cys(77) and Cys(73)-Cys(91) disulfide bonds. alpha LA-IIIA contains Cys(61)-Cys(77), Cys(73)-Cys(91), and Cys(28)-Cys(111) disulfide bonds. The underlying mechanism of the contrasting folding pathways of calcium-bound and calcium-depleted alpha LA is congruent with the cause of diversity of disulfide folding pathways observed among many well-characterized three-disulfide proteins, including bovine pancreatic trypsin inhibitor and hirudin. Our study also reveals novel aspects of the folding mechanism of alpha LA that have not been described previously.

Animals↗