Dynamic changes of proteasome and protective effect of bortezomib, a proteasome inhibitor, in mice with acute pancreatitis

Journal Article · Mon Oct 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.09.066· OSTI ID:23134142

Zhu, Qingtian ^[1]; Lin, Xi ^[1]; Liu, Xinnong; Hou, Tianyu ^[1]; Zhang, Min ^[1]; others, and

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1. Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou (China)

Highlights: • 20s proteasome has a dynamic change in acute pancreatitis induced by caerulein. • Bortezomib, a proteasome inhibitor, alleviates two animal models of AP in mice. • The mechanism appears to involve inhibition of NF-κB signal pathway. • Bortezomib may be a therapeutic candidate for acute pancreatitis. The proteasome is involved in the activation of NF-κB and can regulate the progression of inflammatory diseases. However, the role of proteasome in acute pancreatitis (AP) has not been demonstrated. In this study, we first observed that the protein level and activity of proteasome 20S were increased significantly in pancreatic injury tissues after caerulein-induced mild acute pancreatitis (MAP) induction, which was in consistent with the expression of the NF-κB nucleoprotein and positively correlated with the severity of AP. Then, bortezomib, a classical proteasome inhibitor, was used to intervene the progression of MAP in mice. The results showed that bortezomib administration reduced the serum amylase and lipase levels and mitigated histopathological manifestation of pancreatic injury in mice. Meanwhile, bortezomib decreased the expression of NF-κB p65 nucleoprotein as well as total proteasome 20S protein, and inhibited the activity of 20S in pancreatic tissues. In addition, we found that bortezomib could protect pancreatic acinar cell against necrosis and mitigate the severity of AP in a severe acute pancreatitis model induced by sodium taurocholate hydrate. Taken together, our study for the first time confirmed that the proteasome participated in the pathogenesis of AP and its inhibitor bortezomib could protect against AP in mice.

• OSTI ID: 23134142
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 505; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMYLASE
DIGESTIVE SYSTEM DISEASES
INFLAMMATION
LIPASES
MICE
NECROSIS
NUCLEOPROTEINS
PANCREAS