Linked Life Data

21068199

Source:http://linkedlifedata.com/resource/pubmed/id/21068199

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-24
pubmed:abstractText
Endocrine pancreas from pregnant rats undergoes several adaptations that comprise increase in ?-cell number, mass and insulin secretion, and reduction of apoptosis. Lactogens are the main hormones that account for these changes. Maternal pancreas, however, returns to a nonpregnant state just after the delivery. The precise mechanism by which this reversal occurs is not settled but, in spite of high lactogen levels, a transient increase in apoptosis was already reported as early as the 3rd day of lactation (L3). Our results revealed that maternal islets displayed a transient increase in DNA fragmentation at L3, in parallel with decreased RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation (pAKT), a known prosurvival kinase. Wortmannin completely abolished the prosurvival action of prolactin (PRL) in cultured islets. Decreased pAKT in L3-islets correlated with increased Tribble 3 (TRB3) expression, a pseudokinase inhibitor of AKT. PERK and eIF2? phosphorylation transiently increased in islets from rats at the first day after delivery, followed by an increase in immunoglobulin heavy chain-binding protein (BiP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islets from L3 rats. Chromatin immunoprecipitation (ChIP) and Re-ChIP experiments further confirmed increased binding of the heterodimer ATF4/CHOP to the TRB3 promoter in L3 islets. Treatment with PBA, a chemical chaperone that inhibits UPR, restored pAKT levels and inhibited the increase in apoptosis found in L3. Moreover, PBA reduced CHOP and TRB3 levels in ?-cell from L3 rats. Altogether, our study collects compelling evidence that UPR underlies the physiological and transient increase in ?-cell apoptosis after delivery. The UPR is likely to counteract prosurvival actions of PRL by reducing pAKT through ATF4/CHOP-induced TRB3 expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1522-1490
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R92-100
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21068199-Activating Transcription Factor 4, pubmed-meshheading:21068199-Animals, pubmed-meshheading:21068199-Apoptosis, pubmed-meshheading:21068199-Cells, Cultured, pubmed-meshheading:21068199-Female, pubmed-meshheading:21068199-Insulin, pubmed-meshheading:21068199-Islets of Langerhans, pubmed-meshheading:21068199-Lactation, pubmed-meshheading:21068199-Models, Animal, pubmed-meshheading:21068199-Phosphorylation, pubmed-meshheading:21068199-Prolactin, pubmed-meshheading:21068199-Protein Kinases, pubmed-meshheading:21068199-Proto-Oncogene Proteins c-akt, pubmed-meshheading:21068199-Rats, pubmed-meshheading:21068199-Rats, Wistar, pubmed-meshheading:21068199-Signal Transduction, pubmed-meshheading:21068199-Transcription Factor CHOP, pubmed-meshheading:21068199-Unfolded Protein Response
pubmed:year
2011
pubmed:articleTitle
UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression.
pubmed:affiliation
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't