Linked Life Data

18691157

Source:http://linkedlifedata.com/resource/pubmed/id/18691157

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-11-25
pubmed:abstractText
PON2 (paraoxonase-2) is a ubiquitously expressed antioxidative protein which is largely found in the ER (endoplasmic reticulum). Addressing the cytoprotective functions of PON2, we observed that PON2 overexpression provided significant resistance to ER-stress-induced caspase 3 activation when the ER stress was induced by interference with protein modification (by tunicamycin or dithiothreitol), but not when ER stress was induced by disturbance of Ca(2+) homoeostasis (by thapsigargin or A23187). When analysing the underlying molecular events, we found an activation of the PON2 promoter in response to all tested ER-stress-inducing stimuli. However, only tunicamycin and dithiothreitol resulted in increased PON2 mRNA and protein levels. In contrast, when ER stress was caused by thapsigargin or A23187, we observed a Ca(2+)-dependent active degradation of PON2 mRNA, elicited by its 5'-untranslated region. In addition, thapsigargin and A23187 also induced PON2 protein degradation by a Ca(2+)-dependent calpain-mediated mechanism. Thus we provide evidence that independent mechanisms mediate the degradation of PON2 mRNA and protein after disturbance of Ca(2+) homoeostasis. Furthermore, because Ca(2+)-disturbance induces ER stress, but abrogates the otherwise protective function of PON2 against ER-stress-induced apoptosis, we propose that the underlying cause of ER stress determines the efficacy of putative cellular defence mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
416
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
395-405
pubmed:meshHeading
pubmed-meshheading:18691157-3' Untranslated Regions, pubmed-meshheading:18691157-5' Untranslated Regions, pubmed-meshheading:18691157-Apoptosis, pubmed-meshheading:18691157-Aryldialkylphosphatase, pubmed-meshheading:18691157-Calcimycin, pubmed-meshheading:18691157-Calcium, pubmed-meshheading:18691157-Calpain, pubmed-meshheading:18691157-Cell Line, pubmed-meshheading:18691157-Dithiothreitol, pubmed-meshheading:18691157-Endoplasmic Reticulum, pubmed-meshheading:18691157-Enzyme Inhibitors, pubmed-meshheading:18691157-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18691157-Homeostasis, pubmed-meshheading:18691157-Humans, pubmed-meshheading:18691157-Ionophores, pubmed-meshheading:18691157-Promoter Regions, Genetic, pubmed-meshheading:18691157-RNA Stability, pubmed-meshheading:18691157-Stress, Physiological, pubmed-meshheading:18691157-Thapsigargin, pubmed-meshheading:18691157-Tunicamycin
pubmed:year
2008
pubmed:articleTitle
Protective effect of paraoxonase-2 against endoplasmic reticulum stress-induced apoptosis is lost upon disturbance of calcium homoeostasis.
pubmed:affiliation
Department of Pharmacology, Johannes Gutenberg University, Obere Zahlbacher Strasse 67, D-55131, Mainz, Germany. horke@uni-mainz.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't