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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
Base Sequence
Catalytic Domain
Cell Line, Tumor
Cell Nucleus
Cell Proliferation
Gene Expression Regulation
Gene Knockdown Techniques
Insulin-secreting Cells
Intracellular Space
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
Receptor, Muscarinic M3
Reproducibility Of Results
Ribosomal Protein S6 Kinases, 70-kda
Serum Response Element
Signal Transduction
Transcription Factor Rela
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
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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