mRNA for pancreatic uncoupling protein 2 increases in two models of acute experimental pancreatitis in rats and mice.
Uncoupling-protein 2 (UCP2) is a mitochondrial protein that appears to be involved in cellular oxidant defense and in the regulation of oncotic cell death, both of which are important features of acute pancreatitis. However, UCP2 expression in acute pancreatitis has not been previously reported. In the current experiments, pancreatic gene expression was studied by real-time reverse-transcription/polymerase chain reaction and Northern blots. Two models of acute experimental pancreatitis were investigated: cerulein-induced pancreatitis in mice at two different time points and taurocholate-induced pancreatitis in rats at two degrees of severity. After cerulein administration, acinar injury and leukocyte infiltration was significantly higher at 24 h compared with 12 h after the first injection of cerulein (P<0.05, P<0.005, respectively). UCP2 mRNA was unchanged at 12 h but was nearly 12-fold greater than control levels after 24 h (P<0.001). UCP2 gene expression correlated with acinar injury (r=0.69; P<0.001). By 72 h after taurocholate administration, the severe group had more necrosis than the mild group (P<0.005). Pancreatic UCP2 mRNA was increased fourfold in the severe group compared with controls (P<0.01). UCP2 expression correlated with parenchymal necrosis (r=0.61; P<0.01). Thus, pancreatic UCP2 mRNA increased in two models of acute pancreatitis. The increase in UCP2 gene expression was correlated with the severity of the disease. Up-regulation of UCP2 in the pancreas may be a protective response to oxidative stress, but this increase may also have a negative influence on cellular energy metabolism. Therefore, acinar UCP2 may be an important modifier of the severity of acute pancreatitis.
Segersvärd
Ralf
R
Division of Surgery, Center for Surgical Sciences, K53, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. ralf.segersvard@cfss.ki.se
Rippe
Catarina
C
Duplantier
Marie
M
Herrington
Margery K
MK
Isaksson
Bengt
B
Adrian
Thomas E
TE
Erlanson-Albertsson
Charlotte
C
Permert
Johan
J
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013656:Taurocholic Acid; D013997:Time Factors; D000071246:Uncoupling Protein 2; D015854:Up-Regulation
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D013656:Taurocholic Acid; D002108:Ceruletide