| Involvement of the RNA-binding protein ARE/poly(U)-binding factor 1 (AUF1) in the cytotoxic effects of proinflammatory cytokines on pancreatic beta cells. | |
| | |
MedLine Citation:
|
PMID: 22159912 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
AIMS/HYPOTHESIS: Chronic exposure of pancreatic beta cells to proinflammatory cytokines leads to impaired insulin secretion and apoptosis. ARE/poly(U)-binding factor 1 (AUF1) belongs to a protein family that controls mRNA stability and translation by associating with adenosine- and uridine-rich regions of target messengers. We investigated the involvement of AUF1 in cytokine-induced beta cell dysfunction. METHODS: Production and subcellular distribution of AUF1 isoforms were analysed by western blotting. To test for their role in the control of beta cell functions, each isoform was overproduced individually in insulin-secreting cells. The contribution to cytokine-mediated beta cell dysfunction was evaluated by preventing the production of AUF1 isoforms by RNA interference. The effect of AUF1 on the production of potential targets was assessed by western blotting. RESULTS: MIN6 cells and human pancreatic islets were found to produce four AUF1 isoforms (p42>p45>p37>p40). AUF1 isoforms were mainly localised in the nucleus but were partially translocated to the cytoplasm upon exposure of beta cells to cytokines and activation of the ERK pathway. Overproduction of AUF1 did not affect glucose-induced insulin secretion but promoted apoptosis. This effect was associated with a decrease in the production of the anti-apoptotic proteins, B cell leukaemia/lymphoma 2 (BCL2) and myeloid cell leukaemia sequence 1 (MCL1). Silencing of AUF1 isoforms restored the levels of the anti-apoptotic proteins, attenuated the activation of the nuclear factor-κB (NFκB) pathway, and protected the beta cells from cytokine-induced apoptosis. CONCLUSIONS/INTERPRETATION: Our findings point to a contribution of AUF1 to the deleterious effects of cytokines on beta cell functions and suggest a role for this RNA-binding protein in the early phases of type 1 diabetes. |
| | |
Authors:
|
E Roggli; S Gattesco; A Pautz; R Regazzi |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-13 |
Journal Detail:
|
Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Cell Biology and Morphology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 9, CH-1005, Lausanne, Switzerland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin resistance by increas...
Next Document: Preclinical efficacy of sodium narcistatin to reduce inflammation and joint destruction in rats with...