Downregulation of GRP78 and XIAP is correlated with apoptosis during cerulein-induced acute pancreatitis in rats via regulation of caspase activation

Liu,Yong; Zhou,Zong-Guang; Zhou,Bing; Wang,Rong; Yan,Hui; Li,Yuan

doi:10.3892/mmr.2012.1241

Downregulation of GRP78 and XIAP is correlated with apoptosis during cerulein-induced acute pancreatitis in rats via regulation of caspase activation

Authors:
- Yong Liu
- Zong-Guang Zhou
- Bing Zhou
- Rong Wang
- Hui Yan
- Yuan Li
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Affiliations: Department of Gastroenterological Surgery, West China Hospital, Sichuan University, Sichuan, P.R. China, Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, P.R. China
Published online on: December 18, 2012 https://doi.org/10.3892/mmr.2012.1241
Pages: 725-730
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Our aim in the present study was to investigate the potential roles of the 78-kDa glucose-regulated protein (GRP78) and the X-linked inhibitor of apoptosis protein (XIAP) in the regulation of apoptosis during cerulein-induced acute pancreatitis (CAP). A rat CAP model was induced by injection of cerulein (50 µg/kg), and the severity of CAP was estimated by measuring serum amylase and lipase, pancreatic edema and histological changes. Pancreatic acinar cell apoptosis was determined by terminal-deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) assay, and the expression of GRP78, XIAP and the apoptotic genes caspase-3, -7 and -9 were determined by real‑time quantitative PCR and western blotting. After induction with cerulein, increased serum amylase and lipase, pancreatic edema, inflammation and apoptosis were observed in CAP rats. Furthermore, the mRNA and protein levels of GRP78 and XIAP were significantly downregulated in CAP rats, while the mRNA levels of caspase-3, -7 and -9, as well as the cell apoptotic index were markedly increased when compared with control rats (P<0.05). The expression of GRP78 and XIAP was negatively correlated with caspase expression in CAP (P<0.05). This study suggests that the downregulation of GRP78 and XIAP were correlated with apoptosis in pancreatic acinar cells, and that this may occur through the regulation of caspase activation during CAP.

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