Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice

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dc.contributor.authorMuller, Sarahen_ZA
dc.contributor.authorKaiser, Hannahen_ZA
dc.contributor.authorKruger, Burkharden_ZA
dc.contributor.authorFitzner, Briten_ZA
dc.contributor.authorLange, Falkoen_ZA
dc.contributor.authorBock, Cristin N.en_ZA
dc.contributor.authorNizze, Horsten_ZA
dc.contributor.authorIbrahim, Saleh M.en_ZA
dc.contributor.authorFuellen, Georgen_ZA
dc.contributor.authorWolkenhauer, Olafen_ZA
dc.contributor.authorJaster, Roberten_ZA
dc.date.accessioned2016-03-02T12:28:54Z
dc.date.available2016-03-02T12:28:54Z
dc.date.issued2014-04-10
dc.descriptionPlease cite as follows: Muller, S. et al. 2014. Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice. PLoS ONE, 9(4):e94494, doi:10.1371/journal.pone.0094494.en_ZA
dc.descriptionThe original publication is available at http://journals.plos.org/plosoneen_ZA
dc.description.abstractReactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively) triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of alpha-amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO) in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT) C57BL/6 mice were virtually indistinguishable with respect to disease severity. In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage than WT mice at late time points after the induction of AP (24 h and 7 days, respectively), suggesting retarded regeneration. Furthermore, a higher peak level of alpha-amylase activity and gradually increased MPO levels in pancreatic and lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin activities (in vivo studies) and intraacinar trypsin and elastase activation in response to cerulein treatment (in vitro studies) were not enhanced but even diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished ratio of reduced and oxidized glutathione in serum but no increased ROS levels in pancreatic acini. Together, our data indicate an aggravating effect of UCP2 deficiency on the severity of experimental AP in older but not in young mice. We suggest that increased severity of AP in 12 months old UCP2-/- is caused by an imbalanced inflammatory response but is unrelated to acinar cell functions.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094494
dc.description.versionPublisher's versionen_ZA
dc.format.extent12 pagesen_ZA
dc.identifier.citationMuller, S. et al. 2014. Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice. PLoS ONE, 9(4):e94494, doi:10.1371/journal.pone.0094494.en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0094494
dc.identifier.urihttp://hdl.handle.net/10019.1/98246
dc.language.isoen_ZAen_ZA
dc.publisherPLoSen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectAcute pancreatitisen_ZA
dc.subjectMitochondrial membranesen_ZA
dc.subjectCarrier proteinsen_ZA
dc.subjectOxidative stressen_ZA
dc.titleAge-dependent effects of UCP2 deficiency on experimental acute pancreatitis in miceen_ZA
dc.typeArticleen_ZA
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