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.