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Joel Moss

Publications and source records attributed to Joel Moss.

68 records · Page 4Linked to original sources
PubMed2003

High molecular weight factor in FCS inhibits Helicobacter pylori VacA-binding to its receptor, RPTPbeta, on AZ-521.

VacA, a secretory product of Helicobacter pylori, binds to its cell surface receptor, receptor tyrosine phosphatase (RPTP) beta, leading to cytoplasmic vacuolization of gastric epithelial AZ-521 cells. VacA binding to the cell surface and VacA-dependent vacuolization were inhibited by cell culture media containing fetal calf serum (FCS). The high molecular weight fraction of FCS isolated by Superose 12 gel filtration chromatography inhibited VacA binding, whereas only weak effects were observed with other fractions. These data show that the high molecular weight fraction of FCS inhibits VacA action though its ability to block toxin binding to its receptor, RPTPbeta, on AZ-521 cells.

Bacterial Proteins↗
PubMed2003

STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation.

Interferon-gamma (IFN-gamma) is required for induction of the human nitric oxide synthase-2 (NOS2) gene in lung epithelium. Although the human NOS2 promoter region contains many cytokine-responsive elements, the molecular basis of induction is only partially understood. Here, the major cis-regulatory elements that control IFN-gamma-inducible NOS2 gene transcription in human lung epithelial cells are identified as composite response elements that bind signal transducer and activator of transcription 1 (STAT-1) and activator protein 1 (AP-1), which is comprised of c-Fos, Fra-2, c-Jun, and JunD. Notably, IFN-gamma activation of the human NOS2 promoter is shown to require functional AP-1 regulatory region(s), suggesting a role for AP-1 activation/binding in the IFN-gamma induction of genes. We show that c-Fos interacts with STAT-1 after IFN-gamma activation and the c-Fos/STAT-1 complex binds to the gamma-activated site (GAS) element in close proximity to AP-1 sites located at 4.9 kb upstream of the transcription start site. Taken together, our findings support a model in which a physical interaction between c-Fos and STAT-1 participates in NOS2 gene transcriptional activation.

5' Flanking Region↗
PubMed2002

Endogenous mono-ADP-ribosylation of the free Gbetagamma prevents stimulation of phosphoinositide 3-kinase-gamma and phospholipase C-beta2 and is activated by G-protein-coupled receptors.

We have recently demonstrated that the beta subunit of the heterotrimeric G-proteins is endogenously mono-ADP-ribosylated in intact cells. The modified betagamma heterodimer loses its ability to inhibit calmodulin-stimulated type 1 adenylate cyclase and, remarkably, is de-ADP-ribosylated by a cytosolic hydrolase that completes an ADP-/de-ADP-ribosylation cycle of potential physiological relevance. In the present study, we show that this ADP-ribosylation might indeed be a general mechanism for termination of betagamma signalling, since the ADP-ribosylated betagamma subunit is also unable to activate both phosphoinositide 3-kinase-gamma and phospholipase C-beta2. Moreover, we show that beta subunit ADP-ribosylation is induced by G-protein-coupled receptor activation, since hormone stimulation of Chinese-hamster ovary plasma membranes leads to increases in beta subunit labelling. This occurs when betagamma is in its active heterodimeric conformation, since full inhibition of this modification can be achieved by binding of GDP-alphai3 to the betagamma heterodimer. Taken together, these findings delineate a pathway that arises from the activation of a G-protein-coupled receptor and leads to the inhibition of betagamma activity through its reversible mono-ADP-ribosylation.

Adenosine Diphosphate Ribose↗
PubMed2002

Expression of human telomerase reverse transcriptase in lymphangioleiomyomatosis.

Telomerase synthesizes nucleotide hexameric repeats (telomeres) at the ends of chromosomes, replacing base sequences that are lost from these sites during each mitotic cycle and protecting these ends against the action of exonucleases and ligases. Therefore, telomerase is essential for maintaining cellular replication. To evaluate the role of telomerase in the proliferation of abnormal smooth muscle cells (lymphangioleiomyomatosis [LAM] cells) in LAM, we performed immunostaining and in situ hybridization studies to identify telomerase protein and messenger RNA (mRNA), respectively, in pulmonary (n = 18) and extrapulmonary (n = 4) lesions from 22 women with LAM (14 untreated and 8 treated with progesterone or tamoxifen). Immunoreactivity and hybridization signals for telomerase were observed in 5 to 20% of LAM cells, mostly of the spindle-shaped type, in 21 of the 22 patients, and were less intense in the treated group. Other types of cells were unreactive in both groups. Telomerase colocalized in the same cells with alpha-smooth muscle actin, but only rarely with HMB-45 antibody (a marker for epithelioid LAM cells); colocalization with proliferating cell nuclear antigen was incomplete. The telomerase-positive LAM cells may constitute the sources of renewal of LAM cells. Modulation of telomerase may be involved in the control of LAM cell proliferation.

Adolescent↗
PubMed2002

ADP ribosylation of human neutrophil peptide-1 regulates its biological properties.

In human airways, epithelial cells lining the lumen and intraluminal cells (e.g., polymorphonuclear cells) participate in the innate immune response. These cells secrete or express on their surfaces arginine-specific ADP ribosyltransferases. Defensins, antimicrobial proteins secreted by immune cells, are arginine-rich, leading us to hypothesize that ADP ribosylation could modify their biological activities. We found that an arginine-specific ADP ribosyltransferase-1 present on airway epithelial cells modifies Arg-14 of alpha defensin-1. ADP-ribosylated defensin-1 had decreased antimicrobial and cytotoxic activities but still stimulated T cell chemotaxis and IL-8 release from A549 cells. Further, ADP-ribosylated defensin-1 inhibited cytotoxic and antimicrobial activities of unmodified defensin-1. We identified ADP-ribosylated defensin-1 in bronchoalveolar lavage fluid from smokers but not from nonsmokers, confirming its existence in vivo. Thus, airway mono-ADP-ribosyltransferases could have an important regulatory role in the innate immune response through modification of alpha defensin-1 and perhaps other basic molecules, with alteration of their biological properties.

ADP Ribose Transferases↗
PubMed2002

Cybr, a cytokine-inducible protein that binds cytohesin-1 and regulates its activity.

Cytokines regulate lymphocyte development and differentiation, but precisely how they control these processes is still poorly understood. By using microarray technology to detect cytokine-induced genes, we identified a cDNA encoding Cybr, which was increased markedly in cells incubated with IL-2 and IL-12. The mRNA was most abundant in hematopoietic cells and tissues. The predicted amino acid sequence is similar to that of GRP-1-associated protein (GRASP), a recently identified retinoic acid-induced cytohesin-binding protein. Physical interaction, dependent on the coiled-coil domains of Cybr and cytohesin-1, was demonstrated by coimmunoprecipitation of the overexpressed proteins from 293T cells. Cytohesin-1, in addition to its role in cell adhesion, is a guanine nucleotide-exchange protein activator of ARF GTPases. Acceleration of guanosine 5prime prime or minute-O-(thiotriphosphate) binding to ARF by cytohesin-1 in vitro was enhanced by Cybr. Because the binding protein modified activation of ADP ribosylation factor by cytohesin-1, we designate this cytokine-inducible protein Cybr (cytohesin binder and regulator).

Amino Acid Sequence↗
PubMed2002

Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation.

Kampo formulations are traditional herbal medications used in China and Japan for many centuries to treat diarrheal diseases such as cholera. Our studies were undertaken to identify and verify by chemical synthesis the active components that inhibited cholera toxin (CT), the virulence factor secreted by Vibrio cholerae, the causative agent of cholera. The Kampo formulation, Daio-kanzo-to, inhibited CT activities (i.e., ADP-ribosylation, Chinese hamster ovary cell elongation); in Daio-kanzo-to, Daio (Rhei rhizoma) was responsible for this effect. Among several components purified from Daio extract, rhubarb galloyl-tannin, a compound characterized by a polygallate structure, was the most effective. To define the active component, gallate analogues similar to rhubarb galloyl-tannin were synthesized. These gallate compounds inhibited all CT activities including ADP-ribosylation, elongation of Chinese hamster ovary cells, and importantly, fluid accumulation in ileal loops. Thus, Kampo formulations or their gallate components might be effective adjunctive therapy with oral rehydration solution for the severe diarrhea of cholera.

Adenosine Diphosphate Ribose↗
PubMed2002

Auto-ADP-ribosylation of Pseudomonas aeruginosa ExoS.

Pseudomonas aeruginosa Exoenzyme S (ExoS) is a bifunctional type-III cytotoxin. The N terminus possesses a Rho GTPase-activating protein (GAP) activity, whereas the C terminus comprises an ADP-ribosyltransferase domain. We investigated whether the ADP-ribosyltransferase activity of ExoS influences its GAP activity. Although the ADP-ribosyltransferase activity of ExoS is dependent upon FAS, a 14-3-3 family protein, factor-activating ExoS (FAS) had no influence on the activity of the GAP domain of ExoS (ExoS-GAP). In the presence of NAD and FAS, the GAP activity of full-length ExoS was reduced about 10-fold, whereas NAD and FAS did not affect the activity of the ExoS-GAP fragment. Using [(32)P]NAD, ExoS-GAP was identified as a substrate of the ADP-ribosyltransferase activity of ExoS. Site-directed mutagenesis revealed that auto-ADP-ribosylation of Arg-146 of ExoS was crucial for inhibition of GAP activity in vitro. To reveal the auto-ADP-ribosylation of ExoS in intact cells, tetanolysin was used to produce pores in the plasma membrane of Chinese hamster ovary (CHO) cells to allow the intracellular entry of [(32)P]NAD, the substrate for ADP-ribosylation. After a 3-h infection of CHO cells with Pseudomonas aeruginosa, proteins of 50 and 25 kDa were preferentially ADP-ribosylated. The 50-kDa protein was determined to be auto-ADP-ribosylated ExoS, whereas the 25-kDa protein appeared to represent a group of proteins that included Ras.

ADP Ribose Transferases↗
PubMed2002

Cytohesin-1 in 2001.

Explore the source record for details and available documents.

ADP-Ribosylation Factors↗
PubMed2002

Lymphangioleiomyomatosis: correlation of qualitative and quantitative thin-section CT with pulmonary function tests and assessment of dependence on pleurodesis.

PURPOSE: To explore the relationship between findings at thin-section computed tomography (CT) and pulmonary function tests in lymphangioleiomyomatosis (LAM) and to evaluate the influence of pleurodesis on this relation and the effectiveness of quantitative versus qualitative CT in the assessment of disease severity. MATERIALS AND METHODS: Thirty-seven patients with LAM (17 with pleurodesis) underwent CT and pulmonary function tests. The severity of pulmonary cystic involvement was graded qualitatively by two independent readers and measured quantitatively at CT with a thresholding technique. Relationships between findings at CT and pulmonary function tests and the influence of pleurodesis on these findings were assessed with regression analysis and analysis of covariance. RESULTS: Qualitative ratings had good agreement between observers (kappa = 0.75). Quantitative CT had good repeatability and showed significant correlation with the percent predicted forced expiratory volume in 1 second (FEV(1)%) (r = 0.67, P <.001), percent predicted diffusing capacity of lung for carbon monoxide (DLCO%) (r = 0.48, P <.005), percent predicted ratio of residual volume to total lung capacity (RV/TLC%) (r = -0.65, P <.001), and percent predicted TLC (r = 0.34, P <.04). Quantitative CT results were somewhat better than qualitative CT results. The standard error of the FEV(1)% for the quantitative CT was about 85% of that for the qualitative CT. Pleurodesis had no statistically significant effect on the slope of the regression line between quantitative CT findings, FEV(1)%, and DLCO% (corrected for alveolar volume). The slope between quantitative CT and RV/TLC% was significantly (P =.044) more negative in patients with pleurodesis. CONCLUSION: Qualitative and quantitative CT findings correlate with pulmonary dysfunction over a wide range of disease severity in patients with LAM. Pleurodesis influences the relationship between CT measurements and pulmonary function test results.

Adult↗
PubMed2002

Giles F. Filley Lecture. Genetics and gene expression in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a disease of unknown etiology that is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the lung, which leads to cystic parenchymal destruction and progressive respiratory failure. Recent evidence suggests that the proliferative and invasive nature of LAM cells may be due, in part, to somatic mutations in the TSC2 gene, which has been implicated in the pathogenesis of tuberous sclerosis complex. Here, we describe the clinical and molecular characteristics of LAM, as well as the efforts now under way to understand the genetic and biochemical factors that lead to progressive pulmonary destruction and, ultimately, to lung transplantation or death.

Adult↗