Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice

Reactive 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 af...

Full description

Bibliographic Details
Main Authors:	Müller, Sarah, Kaiser, Hannah, Krüger, Burkhard, Fitzner, Brit, Lange, Falko, Bock, Cristin N., Nizze, Horst, Ibrahim, Saleh M., Fuellen, Georg, Wolkenhauer, Olaf, Jaster, Robert
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983280/

id	pubmed-3983280
recordtype	oai_dc
spelling	pubmed-39832802014-04-15 Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice Müller, Sarah Kaiser, Hannah Krüger, Burkhard Fitzner, Brit Lange, Falko Bock, Cristin N. Nizze, Horst Ibrahim, Saleh M. Fuellen, Georg Wolkenhauer, Olaf Jaster, Robert Research Article Reactive 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. Public Library of Science 2014-04-10 /pmc/articles/PMC3983280/ /pubmed/24721982 http://dx.doi.org/10.1371/journal.pone.0094494 Text en © 2014 Müller et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Müller, Sarah Kaiser, Hannah Krüger, Burkhard Fitzner, Brit Lange, Falko Bock, Cristin N. Nizze, Horst Ibrahim, Saleh M. Fuellen, Georg Wolkenhauer, Olaf Jaster, Robert
spellingShingle	Müller, Sarah Kaiser, Hannah Krüger, Burkhard Fitzner, Brit Lange, Falko Bock, Cristin N. Nizze, Horst Ibrahim, Saleh M. Fuellen, Georg Wolkenhauer, Olaf Jaster, Robert Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice
author_facet	Müller, Sarah Kaiser, Hannah Krüger, Burkhard Fitzner, Brit Lange, Falko Bock, Cristin N. Nizze, Horst Ibrahim, Saleh M. Fuellen, Georg Wolkenhauer, Olaf Jaster, Robert
author_sort	Müller, Sarah
title	Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice
title_short	Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice
title_full	Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice
title_fullStr	Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice
title_full_unstemmed	Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice
title_sort	age-dependent effects of ucp2 deficiency on experimental acute pancreatitis in mice
description	Reactive 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.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983280/
_version_	1612076944933781504

Age-Dependent Effects of UCP2 Deficiency on Experimental Acute Pancreatitis in Mice

Similar Items