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Jing Yang

Publications and source records attributed to Jing Yang.

At least 91 records · Page 5Linked to original sources
PubMed2005

The effect of tripeptide tyroserleutide (YSL) on animal models of hepatocarcinoma.

This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the survival time of mice transplanted with the ascitic fluid-type hepatocarcinoma H22, as well as the inhibitory effect of tyroserleutide on the human hepatocarcinoma Bel-7402 that was transplanted into nude mice. At doses of 80, 20 and 5 microg/kg/d, tyroserleutide significantly prolonged the survival of mice transplanted with H22 tumor cells, producing survival rates of 89%, 39% and 49%, respectively, which were statistically significantly different from the saline group (P < 0.05). YSL, at doses of 80, 160 and 320 microg/kg/d significantly inhibited the growth of the human hepatocarcinoma Bel-7402 tumor in nude mice, producing inhibition of 40%, 64% and 59%, respectively; this inhibition was significantly greater than that by saline (P < 0.05). HE staining and electron microscopy of the pathological changes of the tumor in nude mice showed that YSL changed the structure Bel-7402 tumor cells that were transplanted into nude mice, and also induced tumor cell apoptosis and necrosis, which could be a mechanism by which YSL inhibits the tumor growth in animal models.

Animals↗
PubMed2005

Genotoxicity sensor response correlated with DNA nucleobase damage rates measured by LC-MS.

Responses from "reagentless" DNA-based electrochemical toxicity sensors to DNA alkylating agents styrene oxide (SO), diepoxybutane (DEB), and methyl methanesulfonate (MMS) were compared to formation rates of total alkylated nucleobases in DNA measured by LC-UV-MS. Sensors utilized a catalytic metallopolymer in DNA films previously exposed to the damage agents. To achieve adequate sensitivity, LC-UV-MS analyses were done on DNA in solution reacted with the damage agents, and subsequently hydrolyzed to nucleosides with enzymes. Sensor response correlated well with nucleobase-adduct formation rates obtained by the molecule-specific analyses. Results confirm that the metallopolymer-DNA film sensors can be used to estimate relative DNA damage rates from nucleobase adduct-forming chemicals. Results from both methods correlated well with animal genotoxicity as estimated by TDL(o) values, the lowest dose producing carcinogenicity, in mice and rats. These sensors should be useful for rapid, inexpensive screening of moderately and severely genotoxic new chemicals.

Animals↗
PubMed2005

A critical role for enhanced TGF-alpha and EGFR expression in the initiation of parathyroid hyperplasia in experimental kidney disease.

The parathyroid hyperplasia secondary to kidney disease is associated with enhanced expression of the growth promoter transforming growth factor-alpha (TGF-alpha). TGF-alpha stimulates growth through activation of its receptor, the epidermal growth factor receptor (EGFR), normally expressed in the parathyroid glands. Because enhanced coexpression of TGF-alpha and EGFR causes aggressive cellular growth, these studies utilized highly specific inhibitors of EGFR tyrosine kinase, a step mandatory for TGF-alpha-induced EGFR activation, to assess the contribution of growth signals from enhanced expression of TGF-alpha exclusively or both TGF-alpha and EGFR to the rapid parathyroid growth induced by kidney disease and exacerbated by high-phosphorus (P) and low-calcium (Ca) diets in rats. The enhancement in parathyroid gland weight and proliferating activity (proliferating cell nuclear antigen/Ki67) induced by kidney disease and aggravated by either high P or low Ca intake, within the first week after 5/6 nephrectomy, in rats, coincided with simultaneous increases (2- to 3-fold) in TGF-alpha and EGFR content. Conversely, prevention of the increases in both TGF-alpha and EGFR paralleled the efficacy of either P restriction or high-Ca intake in ameliorating uremia-induced parathyroid hyperplasia. More importantly, suppression of TGF-alpha/EGFR signaling, through prophylactic administration of potent and highly selective inhibitors of ligand-induced EGFR activation, completely prevented both high-P- and low-Ca-induced parathyroid hyperplasia as well as TGF-alpha self-upregulation. Thus enhanced parathyroid TGF-alpha/EGFR expression, self-upregulation, and growth signals occur early in kidney disease, are aggravated by low-Ca and high-P intake, and constitute the main pathogenic mechanism of the severity of parathyroid hyperplasia.

Animals↗
PubMed2005

Gene expression evolves faster in narrowly than in broadly expressed mammalian genes.

Despite much recent interest, it remains unclear what determines the rate of evolution of gene expression. To study this issue we develop a new measure, called "Expression Conservation Index" (ECI), to quantify the degree of tissue-expression conservation between two homologous genes. Applying this measure to a large set of gene expression data from human and mouse, we show that tissue expression tends to evolve rapidly for genes that are expressed in only a limited number of tissues, whereas tissue expression can be conserved for a long time for genes expressed in a large number of tissues. Therefore, expression breadth is an important determinant for evolutionary conservation of tissue expression. In addition, we find a rapid decrease in ECI with the synonymous divergence between duplicate genes, suggesting fast divergence in tissue expression between duplicate genes.

Animals↗
PubMed2005

New enantiomeric polylactide-block-poly(butylene succinate)-block-polylactides: syntheses, characterization and in situ self-assembly.

In situ self-assemblies of new biodegradable triblock PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA have been investigated in acetonitrile solution. At first, two series of PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA, respectively denoted as the P and Q triblock copolyester series, were prepared with fixed PBS block ((overline) M(n,NMR) = 6.9 kDa) and diverse enantiomeric PLLA/PDLA blocks. Further, their chemical structures and thermal properties were characterized by means of titration, nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), polarimeter, wide-angle X-ray diffraction (WAXD) and thermal analytical instruments. When mixing the synthesized enantiomeric copolyester pairs denoted as P(1)/Q(1) - P(8)/Q(8) in acetonitrile solution at 60 degrees C, in situ self-assemblies were found to happen for the P(4)/Q(4) to P(8)/Q(8) pairs, bearing longer enantiomeric PLA block lengths. DSC and WAXD analysis of the self-assembled microparticles demonstrated that PLLA/PDLA racemic crystals were formed for the P(5)/Q(5) - P(8)/Q(8) systems, as evidenced by their melting points over 200 degrees C, and a new X-ray diffraction peak detected at 2theta = 11.8 degrees . Moreover, morphological studies by scanning electron microscopy (SEM) indicated the formation of disk- or platelet-like microparticles. It was noted that the diameters of the microparticles self-assembled in situ decreased from 1.28-1.50 mum down to 480-660 nm, through tailoring the enantiomeric PLA block length. Other factors, such as a central PBS block, the enantiomeric block length and the preparation conditions were suggested to play important roles in the in situ self-assembly of these enantiomeric triblock copolyesters. These results provide a facile way to self-assemble hydrophobic, biodegradable microparticles, through tuning the important van der Waals stereocomplexation interactions between two enantiomeric blocks in solution.

Acetonitriles↗
PubMed2005

Dissociated phenotypes in presenilin transgenic mice define functionally distinct gamma-secretases.

Gamma-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2 within a core complex. This endoproteolytic activity cleaves within transmembrane domains of amyloid-beta precursor protein (APP) and Notch, and familial Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from production of amyloid-beta (Abeta) 40 peptide to greater production of Abeta42. Although studies in PS1/PS2-deficient embryonic cells define overlapping activities for these proteins, in vivo complementation of PS1-deficient animals described here reveals an unexpected spectrum of activities dictated by PS1 and PS2 alleles. Unlike PS1 transgenes, wild-type PS2 transgenes expressed in the mouse CNS support little Abeta40 or Abeta42 production, and FAD PS2 alleles support robust production of only Abeta42. Although wild-type PS2 transgenes failed to rescue Notch-associated skeletal defects in PS1 hypomorphs, a "gained" competence in this regard was apparent for FAD alleles of PS2. The range of discrete and divergent processing activities in mice reconstituted with different PS genes and alleles argues against gamma-secretase being a single enzyme with intrinsically relaxed substrate and cleavage site specificities. Instead, our studies define functionally distinct gamma-secretase variants. We speculate that extrinsic components, in combination with core complexes, may tailor functional variants of this enzyme to their preferred substrates.

Alzheimer Disease↗
PubMed2005

A novel site contributing to growth-arrest-specific gene 6 binding to its receptors as revealed by a human monoclonal antibody.

Gas6 (growth-arrest-specific gene 6) is a vitamin K-dependent protein known to activate the Axl family of receptor tyrosine kinases. It is an important regulator of thrombosis and many other biological functions. The C-terminus of Gas6 binds to receptors and consists of two laminin-like globular domains LG1 and LG2. It has been reported that a Ca2+-binding site at the junction of LG1 and LG2 domains and a hydrophobic patch at the LG2 domain are important for receptor binding [Sasaki, Knyazev, Cheburkin, Gohring, Tisi, Ullrich, Timpl and Hohenester (2002) J. Biol. Chem. 277, 44164-44170]. In the present study, we developed a neutralizing human monoclonal antibody, named CNTO300, for Gas6. The antibody was generated by immunization of human IgG-expressing transgenic mice with recombinant human Gas6 protein and the anti-Gas6 IgG sequences were rescued from an unstable hybridoma clone. Binding of Gas6 to its receptors was partially inhibited by the CNTO300 antibody in a dose-dependent manner. To characterize further the interaction between Gas6 and this antibody, the binding kinetics of CNTO300 for recombinant Gas6 were compared with independently expressed LG1 and LG2. The CNTO300 antibody showed comparable binding affinity, yet different dependence on Ca2+, to Gas6 and LG1. No binding to LG2 was detected. In the presence of EDTA, binding of the antibody to Gas6 was disrupted, but no significant effect of EDTA on LG1 binding was evident. Further epitope mapping identified a Gas6 peptide sequence recognized by the CNTO300 antibody. This peptide sequence was found to be located at the LG1 domain distant from the Ca2+-binding site and the hydrophobic patch. Co-interaction of Gas6 with its receptor and CNTO300 antibody was detected by BIAcore analysis, suggesting a second receptor-binding site on the LG1 domain. This hypothesis was further supported by direct binding of Gas6 receptors to an independently expressed LG1 domain. Our results revealed, for the first time, a second binding site for Gas6-receptor interaction.

Amino Acid Sequence↗
PubMed2005

Different firing patterns induced by veratridine and aconitine in injured dorsal root ganglion neurons.

Ectopic spontaneous activity originated from the injured dorsal root ganglion (DRG) neurons in rats was recorded through single dorsal root fiber. The firing patterns induced by veratridine and aconitine, inhibitors of inactivation gate of sodium channel operating on different binding sites, were compared. In the same neuron, veratridine (1.5 approximately 5.0 micromol/L) caused slow wave oscillations of interspike intervals (ISIs), while aconitine (10 approximately 200 micromol/L) caused tonic firing. Moreover, even if the background firing patterns were various and the reagent concentrations used were different, veratridine and aconitine still induced slow wave oscillations and tonic firing patterns, respectively. The results suggest that veratridine and aconitine induce different firing patterns in injured DRG neurons, which may relate to their inhibitory effects on different binding sites of the sodium channel.

Aconitine↗
PubMed2005

HBVPathDB: a database of HBV infection-related molecular interaction network.

AIM: To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection. METHODS: The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML). RESULTS: We present the first version of HBVPathDB, which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1 050 molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search, unitized search-are supported by the search engine of the database. The database is freely available at http://www.bio-inf.net/HBVPathDB/HBV/. CONCLUSION: The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing, visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.

Databases, Genetic↗
PubMed2005

Neural crest induction by the canonical Wnt pathway can be dissociated from anterior-posterior neural patterning in Xenopus.

While Wnt signaling is known to be involved in early steps of neural crest development, the mechanism remains unclear. Because Wnt signaling is able to posteriorize anterior neural tissues, neural crest induction by Wnts has been proposed to be an indirect consequence of posteriorization of neural tissues rather than a direct effect of Wnt signaling. To address the relationship between posteriorization and neural crest induction by Wnt signaling, we have used gain of function and loss of function approaches in Xenopus to modulate the level of Wnt signaling at multiple points in the pathway. We find that modulating the level of Wnt signaling allows separation of neural crest induction from the effects of Wnts on anterior-posterior neural patterning. We also find that activation of Wnt signaling induces ectopic neural crest in the anterior region without posteriorizing anterior neural tissues. In addition, Wnt signaling induces neural crest when its posteriorizing activity is blocked by inhibition of FGF signaling in neuralized explants. Finally, depletion of beta-catenin confirms that the canonical Wnt pathway is required for initial neural crest induction. While these observations do not exclude a role for posteriorizing signals in neural crest induction, our data, together with previous observations, strongly suggest that canonical Wnt signaling plays an essential and direct role in neural crest induction.

Animals↗
PubMed2005

Endofacial competitive inhibition of glucose transporter-4 intrinsic activity by the mitogen-activated protein kinase inhibitor SB203580.

The translocation of glucose transporter-4 (GLUT4) to the cell surface is a complex multistep process that involves movement of GLUT4 vesicles from a reservoir compartment, and docking and fusion of the vesicles with the plasma membrane. It has recently been proposed that a p38 mitogen-activated protein kinase (MAPK)-dependent step may lead to intrinsic activation of the transporters exposed at the cell surface. In contrast to data obtained in muscle and adipocyte cell lines, we found that no insulin activation of p38 MAPK occurred in rat adipose cells. However, the p38 MAPK inhibitor SB203580 consistently inhibited transport activity after preincubation with the adipose cells. These apparently contradictory findings led us to hypothesize that the inhibitor may have a direct effect on the transport catalytic activity of GLUT4 that was independent of inhibition of the kinase. Kinetic analysis of 3-O-methyl-d-glucose transport activity revealed that SB203580 was a noncompetitive inhibitor of zero-trans (substrate outside but not inside) transport, but was a competitive inhibitor of equilibrium-exchange (substrate inside and outside) transport. This pattern of inhibition of GLUT4 was also observed with cytochalasin B. The pattern of inhibition is consistent with interaction at the endofacial surface, but not the exofacial surface of the transporter. Occupation of the endofacial substrate site reduces maximum velocity under zero-trans conditions, because return of the substrate site to the outside is blocked, and no substrate is present inside to displace the inhibitor. Under equilibrium-exchange conditions, internal substrate competitively displaces the inhibitor, and the transport K(m) is increased.

Adipocytes↗
PubMed2005

Characterization of functional urotensin II receptors in human skeletal muscle myoblasts: comparison with angiotensin II receptors.

The properties of urotensin II (U-II) receptor (UT receptor) and angiotensin II (ANG II) receptor (AT receptor) in primary human skeletal myoblasts (HSMM) and differentiated skeletal myotubes (HSMMT) were characterized. Radiolabeled U-II and ANG II bound specifically to HSMM with Kd's of 0.31 nM (2311 receptors/cell) and 0.61 nM (18,257 receptors/cell), respectively. The cyclic segment of U-II peptide, CFWKYC, was the minimal sequence required for binding, with the WKY residues essential. Inhibitor studies suggested AT1 is the predominant ANG II receptor. After radioligand binding, under conditions designed to minimize receptor internalization, half the bound U-II was resistant to acid washing suggesting that U-II binds tightly to its receptor in a quasi-irreversible fashion. The AT1 receptor-bound radioligand was completely removed under the same conditions. RT-PCR detected the expression of mRNAs for UT and AT1 receptors. Western blotting showed that U-II and ANG II signaled via ERK1/2 kinase. UT receptor was not lost upon differentiation into myotubes since both mRNA for UT receptor and U-II binding were still present. ANG II receptors were also present as shown by ANG II-induced calcium mobilization.

Angiotensin II↗
PubMed2005

Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear translocation of telomerase reverse transcriptase protein by activating nuclear factor-kappaB p65 in human nasopharyngeal carcinoma cells.

Sustained proliferation of cancer cells requires that telomerase maintain chromosomal stability and prolong telomere length-regulated cell replication. Human telomerase reverse transcriptase (hTERT), the human telomerase catalytic subunit, and also the key determinant of the enzymatic activity of human telomerase, is regulated both at the transcriptional level and via phosphorylation and translocation. In this study, we show that latent membrane protein 1 (LMP1), the principal oncoprotein of Epstein-Barr virus (EBV), modulates telomerase activity by inducing the direct binding of hTERT to nuclear factor kappaB (NF-kappaB) p65 and translocation of both proteins from the cytoplasm to the nucleus in nasopharyngeal carcinoma cells (NPC). Conversely, a NF-kappaB nuclear translocation inhibitor, (benzylcarbonyl)-Leu-Leu-phenylalaninal (Z-LLF-CHO), and a dominant negative mutant of inhibitor of NFkappaB (IkappaBalpha), can block LMP1-induced hTERT nuclear translocation. These studies suggest a novel function of LMP1 and confirm that NF-kappaB plays an important role in regulating the activation and nuclear translocation of telomerase in NPC cells.

Antigens, Viral↗
PubMed2005

Insulin signaling meets vesicle traffic of GLUT4 at a plasma-membrane-activated fusion step.

A hypothesis that accounts for most of the available literature on insulin-stimulated GLUT4 translocation is that insulin action controls the access of GLUT4 vesicles to a constitutively active plasma-membrane fusion process. However, using an in vitro fusion assay, we show here that fusion is not constitutively active. Instead, the rate of fusion activity is stimulated 8-fold by insulin. Both the magnitude and time course of stimulated in vitro fusion recapitulate the cellular insulin response. Fusion is cell cytoplasm and SNARE dependent but does not require cell cytoskeleton. Furthermore, insulin activation of the plasma-membrane fraction of the fusion reaction is the essential step in regulation. Akt from the cytoplasm fraction is required for fusion. However, the participation of Akt in the stimulation of in vitro fusion is dependent on its in vitro recruitment onto the insulin-activated plasma membrane.

Adenosine Triphosphate↗
PubMed2005

Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells.

OBJECTIVE: The aim of this study is to investigate the signaling pathways and their roles in the differentiation of immature monocyte-derived dendritic cells (MoDCs). METHODS: MoDCs were generated from peripheral blood monocytes (PBMCs) using the standard protocols. Various kinase inhibitors, including SB203580, PD98059, and LY294002 and Wortmannin, or p38 activator were added at the beginning of the cultures. After 7 days of culture, immature MoDCs were harvested and analyzed for their surface expression of relevant molecules and the fraction of apoptotic cells by flow cytometry. Western blots were used to analyze mitogen-activated protein kinase (MAPK), NF-kappaB, Raf, mitogen-induced extracellular kinase (MEK), and AKT expression by cultured cells. NF-kappaB was also analyzed by electrophoretic mobility shift assay. Allogeneic MLR was used to examine the capacity of MoDCs to activate allogeneic T cells. RESULTS: The present study shows that the differentiation of immature MoDCs was accompanied by phosphorylation of AKT, Raf, MEK, extracellular signal-related kinase (ERK), and NF-kappaB activity. Inhibiting PI3K or MEK retarded the differentiation of immature MoDCs and induced apoptosis in 10 to 30% of the cultured cells, while inhibiting both PI3K and MEK resulted in apoptosis in 70% of the cells. Surprisingly, inhibiting p38 enhanced the phosphorylation of ERK and NF-kappaB activity and led to an enhanced upregulation, compared with control cells, of expression of dendritic cell (DC)-related adhesion and costimulatory molecules and antigen presentation capacity. CONCLUSIONS: Our results indicate that the Raf/MEK/ERK and PI3K/AKT signaling pathways play critical roles in the differentiation and survival of immature MoDCs. Moreover, this study also demonstrates that activated p38 is detrimental to the differentiation of immature MoDCs.

Anisomycin↗
PubMed2005

Direct interaction of myosin regulatory light chain with the NMDA receptor.

NMDA receptors interact with a variety of intracellular proteins at excitatory synapses. In this paper we show that myosin regulatory light chain (RLC) isolated from mouse brain is a NMDA receptor-interacting protein. Myosin RLC bound directly to the C-termini of both NMDA receptor 1 (NR1) and NMDA receptor 2 (NR2) subunits, rendering the interaction of myosin RLC with NMDA receptors distinct from that of calmodulin which is considered a NR1-interacting protein. Myosin RLC co-localized with NR1 in the dendritic spines of isolated hippocampal neurons, and was co-immunoprecipitated from brain extracts in a complex with NR1, NR2A, NR2B, PSD-95, Adaptor protein-2 and myosin II heavy chain. The C0 region of NR1 was necessary and sufficient for binding myosin RLC. Ca2+/calmodulin, but not calmodulin alone, displaced recombinant myosin RLC from the carboxy tail of NR1 indicating that myosin RLC and Ca2+/calmodulin can compete for a common binding site on NR1 in vitro. Myosin RLC is the only known substrate for myosin regulatory light chain kinase, which has recently been shown to modulate NMDA receptor function in isolated hippocampal neurons. Our results suggest that an additional level of NMDA receptor regulation may be mediated via a direct interaction with a light chain of myosin II. Thus, myosin RLC-NMDA receptor interactions may contribute to the contractile and motile forces that are placed upon NMDA receptor subunits during changes associated with synaptic plasticity and neural morphogenesis.

Amino Acid Sequence↗