1,010,859 research outputs found

    Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

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    The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

    The Presence of GC-C in Extracellular Vesicles Secreted by Colorectal Cancer Cells

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    Background: Guanylyl Cyclase C (GC-C) is a membrane-bound protein found on intestinal epithelial cells involved in the activation of CFTR. This protein has previously been involved in the development of colorectal cancer. Extracellular vesicles (EVs) are bilayered vesicles of varying size (30 to 1,000 + nm in diameter) that believed to be secreted by all cells in the human body. In the past decade, EVs have garnered attention due to their impact in the field of oncology, where they have been shown to potentially serve as biomarkers for various cancers. In this study, we looked at the EVs secreted by GC-C+ and GC-C- cell lines. We expected GC-C to be present on the EVs secreted by GC-C+ cell lines and that this finding may intake a role for GC-C at tissues distal to the intestinal epithelial cells. Methods: GC-C+ cells lines (T84 and CT26-hGCC) and GC-C- cell lines (SW480 and CT26-WT) were cultured and their media was harvested, then ultracentrifuged to extract the EVs from the media. These EVs were then checked for the presence and absence of various markers (GC-C, Calnexin, TSG101) via Western Blot. Exosome size was assessed via NTA to further provide evidence for the identity of these EVs. Results: Western blot confirmed the presence of TSG101 in both EV types samples, as well as the presence of GC-C in EVs derived from GC-C+ cell lines, but not from GC-C- cell lines. Calnexin was found to be absent in EV samples, excluding the possibility of lysate contamination. NTA analysis confirmed the correct size for the exosomes in sample. Discussion: This study assessed the contents of EVs secreted by colorectal cancer cell lines. Our findings indicate the presence of GC-C on exosomes and microvesicles. Further studies will need to be conducted in order to assess the function of these GC-C+ EVs in the setting of colorectal cancer

    The Globular Cluster Population of NGC 7457: Clues to the Evolution of Field S0 Galaxies

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    In this paper we present the results of a wide-field imaging study of the globular cluster (GC) system of the field S0 galaxy NGC 7457. To derive the global properties of the GC system, we obtained deep BVR images with the WIYN 3.5 m telescope and Minimosaic Imager and studied the GC population of NGC 7457 to a projected radius of approximately 30 kpc. Our ground-based data were combined with archival and published Hubble Space Telescope data to probe the properties of the GC system close to the galaxy center and reduce contamination in the GC candidate sample from foreground stars and background galaxies. We performed surface photometry of NGC 7457 and compared the galaxy's surface brightness profile with the surface density profile of the GC system. The profiles have similar shapes in the inner 1 arcminute (3.9 kpc), but the GC system profile appears to flatten relative to the galaxy light at larger radii. The GC system of NGC 7457 is noticeably elliptical in our images; we measure an ellipticity of 0.66 +/- 0.14 for the GC distribution, which is consistent with our measured ellipticity of the galaxy light. We integrated the radial surface density profile of the GC system to derive a total number of GCs N_GC = 210 +/- 30. The GC specific frequency normalized by the galaxy luminosity and mass are S_N = 3.1 +/- 0.7 and T = 4.8 +/- 1.1, respectively. Comparing the derived GC system properties and other empirical data for NGC 7457 to S0 formation scenarios suggests that this field S0 galaxy may have formed in an unequal-mass merger.Comment: 40 pages, 10 figures, accepted for publication in The Astrophysical Journa

    The Globular Cluster System of M60 (NGC 4649). II. Kinematics of the Globular Cluster System

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    We present a kinematic analysis of the globular cluster (GC) system in the giant elliptical galaxy (gE) M60 in the Virgo cluster. Using the photometric and spectroscopic database of 121 GCs (83 blue GCs and 38 red GCs), we have investigated the kinematics of the GC system. We have found that the M60 GC system shows a significant overall rotation. The rotation amplitude of the blue GCs is slightly smaller than or similar to that of the red GCs, and their angles of rotation axes are similar. The velocity dispersions about the mean velocity and about the best fit rotation curve for the red GCs are marginally larger than those for the blue GCs. Comparison of observed stellar and GC velocity dispersion profiles with those calculated from the stellar mass profile shows that the mass-to-light ratio should be increased as the galactocentric distance increases, indicating the existence of an extended dark matter halo. The entire sample of GCs in M60 is found to have a tangentially biased velocity ellipsoid unlike the GC systems in other gEs. Two subsamples appear to have different velocity ellipsoids. The blue GC system has a modest tangentially biased velocity ellipsoid, while the red GC system has a modest radially biased or an isotropic velocity ellipsoid. From the comparison of the kinematic properties of the M60 GC system to those of other gEs (M87, M49, NGC 1399, NGC 5128, and NGC 4636), it is found that the velocity dispersion of the blue GC system is similar to or larger than that of the red GC system except for M60, and the rotation of the GC system is not negligible. The entire sample of each GC system shows an isotropic velocity ellipsoid except for M60, while the subsamples show diverse velocity ellipsoids. We discuss the implication of these results for the formation models of the GC system in gEs.Comment: 48 pages, 16 figures. To appear in Ap