Linked Life Data

18492819

Source:http://linkedlifedata.com/resource/pubmed/id/18492819

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-5-21
pubmed:abstractText
Exposure of pancreatic beta-cells to long-chain fatty acids leads to the activation of some components of the endoplasmic reticulum (ER) stress pathway and this mechanism may underlie the ability of certain fatty acids to promote beta-cell death. We have studied ER stress in BRIN-BD11 beta-cells exposed to either the saturated fatty acid palmitate (C16:0) or the monounsaturated palmitoleate (C16:1). Palmitate (0.025-0.25 mM) induced the expression of various markers of the RNA-dependent protein kinase-like ER eukaryotic initiation factor 2 alpha (eIF2 alpha) kinase (PERK)-dependent pathway of ER stress (phospho-eIF2 alpha; ATF4, activating transcription factor 4 and C/EBP homologous protein (CHOP-10)) although it failed to promote the expression of the ER chaperone GRP78. By contrast, palmitoleate did not induce any markers of the ER stress pathway even at concentrations as high as 1 mM. When palmitate and palmitoleate were added in combination, a marked attenuation of the ER stress response occurred. Under these conditions, the levels of phospho-eIF2 alpha, ATF4 and CHOP-10 were reduced to less than those found in control cells. Palmitoleate also attenuated the ER stress response to the protein glycosylation inhibitor, tunicamycin, and improved the viability of the cells exposed to this agent. Exposure of the BRIN-BD11 cells to the protein phosphatase inhibitor, salubrinal, in the absence of fatty acids resulted in increased eIF2 alpha phosphorylation but this was abolished by co-incubation with palmitoleate. We conclude that saturated fatty acids activate components of the PERK-dependent ER stress pathway in beta-cells, ultimately leading to increased apoptosis. This effect is antagonised by monounsaturates that may exert their anti-apoptotic actions by regulating the activity of one or more kinase enzymes involved in mediating the phosphorylation of eIF2 alpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 4, http://linkedlifedata.com/resource/pubmed/chemical/Atf4 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Ddit3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-2, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Monounsaturated, http://linkedlifedata.com/resource/pubmed/chemical/PERK kinase, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP, http://linkedlifedata.com/resource/pubmed/chemical/Tunicamycin, http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase, http://linkedlifedata.com/resource/pubmed/chemical/palmitoleic acid
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1479-6805
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
197
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
553-63
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Differential regulation of the endoplasmic reticulum stress response in pancreatic beta-cells exposed to long-chain saturated and monounsaturated fatty acids.
pubmed:affiliation
Peninsula Medical School, Institute of Biomedical and Clinical Science, John Bull Building, Plymouth PL6 8BU, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't