GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Systemic Delivery of Bioactive Glucagon-Like Peptide 1 after Adenoviral-Mediated Gene Transfer in the Murine Salivary Gland
    The Endocrine Society ; 2010
    In:  Endocrinology Vol. 151, No. 9 ( 2010-09-01), p. 4566-4572
    Details
    In: Endocrinology, The Endocrine Society, Vol. 151, No. 9 ( 2010-09-01), p. 4566-4572
    Abstract: An adenoviral (Ad) vector that expresses bioactive glucagon-like peptide 1 (GLP-1) was generated, and its effectiveness at modulating glucose homeostasis was evaluated after transduction of murine salivary glands. The construct was engineered with the signal sequence of mouse GH to direct the peptide into the secretory pathway, followed by a furin cleavage site and the GLP-1(7–37) sequence encoding an Ala to Gly substitution at position 8 to achieve resistance to degradation. When expressed in Neuro2A and COS7 cells, an active form of GLP-1 was specifically detected by RIA in the conditioned medium of transduced cells, showed resistance to degradation by dipeptidyl-peptidase IV, and induced the secretion of insulin from NIT1 pancreatic β-cells in vitro. In vivo studies demonstrated that healthy mice transduced with Ad-GLP-1 in both submandibular glands had serum GLP-1 levels approximately 3 times higher than mice transduced with the control Ad-luciferase vector. In fasted animals, serum glucose levels were similar between Ad-GLP-1 and Ad-luciferase transduced mice in keeping with GLP-1’s glucose-dependent action. However, when challenged with glucose, Ad-GLP-1 transduced mice cleared the glucose significantly faster than control mice. In an animal model of diabetes induced by alloxan, progression of hyperglycemia was significantly attenuated in mice given the Ad-GLP-1 vector compared with control mice. These studies demonstrate that the bioactive peptide hormone, GLP-1, normally secreted from endocrine cells in the gut through the regulated secretory pathway, can be engineered for secretion into the circulatory system from exocrine cells of the salivary gland to affect glucose homeostasis.
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    URL: Article
    DOI: 10.1210/en.2010-0193
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2010
    detail.hit.zdb_id: 2011695-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Aquaporin 1 Is Important for Maintaining Secretory Granule Biogenesis in Endocrine Cells
    The Endocrine Society ; 2008
    In:  Molecular Endocrinology Vol. 22, No. 8 ( 2008-08-01), p. 1924-1934
    Details
    In: Molecular Endocrinology, The Endocrine Society, Vol. 22, No. 8 ( 2008-08-01), p. 1924-1934
    Abstract: Aquaporins (AQPs), a family of water channels expressed in epithelial cells, function to transport water in a bidirectional manner to facilitate transepithelial fluid absorption and secretion. Additionally, AQP1 and AQP5 are found in pancreatic zymogen granules and synaptic vesicles and are involved in vesicle swelling and exocytosis in exocrine cells and neurons. Here, we show AQP1 is in dense-core secretory granule (DCSG) membranes of endocrine tissue: pituitary and adrenal medulla. The need for AQP1 in endocrine cell function was examined by stable transfection of AQP1 antisense RNA into AtT20 cells, a pituitary cell line, to down-regulate AQP1 expression. These AQP1-deficient cells showed more than 60% depletion of DCSGs and significantly decreased DCSG protein levels, including proopiomelanocotin/pro-ATCH and prohormone convertase 1/3, but not non-DCSG proteins. Pulse-chase studies revealed that whereas DCSG protein synthesis was unaffected, approximately 50% of the newly synthesized proopiomelanocortin was degraded within 1 h. Low levels of ACTH were released upon stimulation, indicating that the small number of DCSGs that were made in the presence of the residual AQP1 were functionally competent for exocytosis. Analysis of anterior pituitaries from AQP1 knockout mice showed reduced prohormone convertase 1/3, carboxypeptidase E, and ACTH levels compared to wild-type mice demonstrating that our results observed in AtT20 cells can be extended to the animal model. Thus, AQP1 is important for maintaining DCSG biogenesis and normal levels of hormone secretion in pituitary endocrine cells.
    Type of Medium: Online Resource
    ISSN: 0888-8809 , 1944-9917
    URL: Article
    DOI: 10.1210/me.2007-0434
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 1492112-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Carboxypeptidase E and Secretogranin III Coordinately Facilitate Efficient Sorting of Proopiomelanocortin to the Regulated Secretory Pathway in AtT20 Cells
    The Endocrine Society ; 2016
    In:  Molecular Endocrinology Vol. 30, No. 1 ( 2016-01-01), p. 37-47
    Details
    In: Molecular Endocrinology, The Endocrine Society, Vol. 30, No. 1 ( 2016-01-01), p. 37-47
    Type of Medium: Online Resource
    ISSN: 0888-8809 , 1944-9917
    URL: Article
    DOI: 10.1210/me.2015-1166
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2016
    detail.hit.zdb_id: 1492112-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 4780: An antisense-based approach to induce anti-tumorigenic variants of MET receptor
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4780-4780
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4780-4780
    Abstract: Rational: Aberrant activity of MET receptor, a receptor tyrosine kinase (RTK), is implicated in various forms of cancer. Moreover, functional crosstalk of MET with other RTKs has been reported in tumors and MET has emerged both as a driver and as a primary mechanism of resistance, thus, making MET an attractive target for cancer therapeutics. Aim: Recently, we have described natural soluble decoy variants for multiple RTKs (sdRKTs), including MET, which can antagonize RTK signaling by ligand sequestration and non-functional dimerization. These isoforms can be generated via intronic polyadenylation (IPA) of RTK’s pre-mRNA in a U1-snRNP dependent manner. Our aim is to activate IPA in MET pre-mRNA using antisense compounds and to increase mRNA variants that express dominant-negative soluble decoy MET (sdMET). Methods: Identify actionable IPA sites within introns upstream of the transmembrane-coding exon. Express potential sdMET isoforms and characterize their biological properties. For sdMET isoforms with inhibitory functions, anti-sense compounds are utilized to block the upstream U1 binding site, activate IPA sites, and thus increase expression of sdMET variants in MET-dependent cancer cells. Results: Ectopically expressed sdMET isoforms are secreted into the culture medium. When then added to MET-expressing cells, sdMET variants functioned in a dominant-negative manner over full length MET (FL-MET) and suppressed activation of AKT and MAPK pathways. Moreover, antisense compounds that induce IPA effectively convert oncogenic FL-MET into sdMET variants in multiple cell lines, leading to suppression of downstream pathways and dramatic reduction in cell viability of MET-dependent cells. Conclusion: Most sdMET isoforms are secreted into extracellular space and have inhibitory function. Our anti-sense approach induces IPA, generates truncated sdMET variants at the expense of FL-MET and efficiently blocks FL-MET’s biological activity. Citation Format: Trushar Rathod, Luca Cartegni. An antisense-based approach to induce anti-tumorigenic variants of MET receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4780.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-4780
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    p53Ψ is a transcriptionally inactive p53 isoform able to reprogram cells toward a metastatic-like state
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 32 ( 2014-08-12)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 32 ( 2014-08-12)
    Abstract: Although much is known about the underlying mechanisms of p53 activity and regulation, the factors that influence the diversity and duration of p53 responses are not well understood. Here we describe a unique mode of p53 regulation involving alternative splicing of the TP53 gene. We found that the use of an alternative 3′ splice site in intron 6 generates a unique p53 isoform, dubbed p53Ψ. At the molecular level, p53Ψ is unable to bind to DNA and does not transactivate canonical p53 target genes. However, like certain p53 gain-of-function mutants, p53Ψ attenuates the expression of E-cadherin, induces expression of markers of the epithelial-mesenchymal transition, and enhances the motility and invasive capacity of cells through a unique mechanism involving the regulation of cyclophilin D activity, a component of the mitochondrial inner pore permeability. Hence, we propose that p53Ψ encodes a separation-of-function isoform that, although lacking canonical p53 tumor suppressor/transcriptional activities, is able to induce a prometastatic program in a transcriptionally independent manner.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1321640111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...