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http://repositorio.unicamp.br/jspui/handle/REPOSIP/198896
Type: | Artigo de periódico |
Title: | Requirement Of Nf-kappab Signalling Pathway For Modulation Of The Cholinergic Muscarinic M3 Receptor Expression By Ingap-pp In Insulin-producing Cells. |
Author: | Paula, Flavia M M Barbosa, Helena C L Carneiro, Everardo M Persaud, Shanta J Gagliardino, Juan J Boschero, Antonio C Souza, Kleber L A |
Abstract: | The pentadecapeptide comprising the 104-118 amino acid sequence of the ilotropin-derived Reg3-related islet neogenesis-associated protein (INGAP-PP) has been implicated in beta cell neogenesis and enhancement of insulin secretion in pancreatic islets. The aim of this study was to investigate intracellular pathways by which INGAP-PP signals in insulin-producing cells. Treatment with INGAP-PP increased insulin secretion and intracellular calcium levels in MIN6 cells. INGAP-PP exposure activated c-Myc, serum and particularly nuclear factor-kappaB (NF-kappaB) response elements in insulin-producing cells (1.7+/-0.1, 1.8+/-0.1, 2.4+/-0.3 for RINm5F, and 1.3+/-0.1, 1.3+/-0.1 and 1.6+/-0.1 fold for MIN6 cells compared to controls, respectively). There was an increase in the proliferation rate of viable cells (162+/-17% for RINm5F and 155+/-13% for MIN6) that was accompanied by an increase in proliferating cell nuclear antigen (PCNA) protein expression (187+/-19% and 170+/-8% for RINm5F and MIN6 cells respectively) following INGAP-PP treatment. INGAP-PP increased the expression of the muscarinic M(3) receptor subtype (169+/-4% for RINm5F and 222+/-20% for MIN6 cells). Activation of multiple serum response elements by foetal calf serum also increased muscarinic M(3) receptor expression (173+/-9% for RINm5F and 140+/-7% for MIN6 cells). The blockade of NF-kappaB signalling pathway strongly decreased muscarinic M(3) receptor expression in response to both stimuli. In summary, a network of intracellular signals that includes activation of c-Myc signalling pathway and increased PCNA expression might be related to the increased proliferation rate of insulin-producing cells following incubation with INGAP-PP. NF-kappaB signalling plays an essential role in controlling the expression of the muscarinic M(3) receptor. |
Subject: | Acetylcholine Active Transport, Cell Nucleus Amino Acid Sequence Animals Base Sequence Carbachol Catalytic Domain Cell Line, Tumor Cell Nucleus Cell Proliferation Cytokines Gene Expression Regulation Gene Knockdown Techniques Insulin-secreting Cells Intracellular Space Mice Molecular Sequence Data Peptide Fragments Phosphatidylinositol 3-kinases Proliferating Cell Nuclear Antigen Proto-oncogene Proteins C-akt Proto-oncogene Proteins C-myc Rna, Small Interfering Rats Receptor, Muscarinic M3 Reproducibility Of Results Ribosomal Protein S6 Kinases, 70-kda Serum Response Element Signal Transduction Transcription Factor Rela Up-regulation |
Citation: | European Journal Of Pharmacology. v. 642, n. 1-3, p. 37-46, 2010-Sep. |
Rights: | fechado |
Identifier DOI: | 10.1016/j.ejphar.2010.05.056 |
Address: | http://www.ncbi.nlm.nih.gov/pubmed/20541544 |
Date Issue: | 2010 |
Appears in Collections: | Unicamp - Artigos e Outros Documentos |
Files in This Item:
File | Size | Format | |
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pmed_20541544.pdf | 1.32 MB | Adobe PDF | View/Open |
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