Heat Shock Proteins and Autophagy in Rats with Cerulein-Induced Acute Pancreatitis
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Background/Aims: Heat shock proteins (HSPs) protect rats from cerulein-induced acute pancreatitis (AP) by preventing the subcellular redistribution of cathepsin B and the activation of trypsinogen. Autophagy plays a critical role in the secretion of digestive enzymes and triggering of ceruleininduced AP via the colocalization of trypsinogen and lysosomes. Therefore, using a rat cerulein-induced AP model,we investigated whether HSPs prevent AP by regulating autophagy. Methods: Twelve hours after fed standard laboratory chow and water, the experimental groups (cerulein,water-immersion [WI]-cerulein and heat-shock [HS]-cerulein)and the control groups (control, WI, and HS) received one intraperitoneal injection of cerulein (50 μg/kg) or saline,respectively. All of the rats were sacrifi ced at 6 hours after injection. The severity of the AP was assessed based on the serum amylase level and the histological and electron microscopy findings. Western blotting was also performed for HSP60/70 and LC3B-II. Results: WI and HS induced HSP60and HSP70, respectively. The induced HSP60/70 effectively prevented the development of cerulein-induced AP. Autophagy developed in the rats with cerulein-induced AP and was documented by the expression of LC3-II and electron microscopy fi ndings. The WI-stressed rats and HS-treated rats did not develop cerulein-induced autophagy. Conclusions: HSPs exert protective effects against cerulein-induced AP in rats by inhibiting autophagy.
Abstract
Background/Aims: Heat shock proteins (HSPs) protect rats from cerulein-induced acute pancreatitis (AP) by preventing the subcellular redistribution of cathepsin B and the activation of trypsinogen. Autophagy plays a critical role in the secretion of digestive enzymes and triggering of ceruleininduced AP via the colocalization of trypsinogen and lysosomes. Therefore, using a rat cerulein-induced AP model,we investigated whether HSPs prevent AP by regulating autophagy. Methods: Twelve hours after fed standard laboratory chow and water, the experimental groups (cerulein,water-immersion [WI]-cerulein and heat-shock [HS]-cerulein)and the control groups (control, WI, and HS) received one intraperitoneal injection of cerulein (50 μg/kg) or saline,respectively. All of the rats were sacrifi ced at 6 hours after injection. The severity of the AP was assessed based on the serum amylase level and the histological and electron microscopy findings. Western blotting was also performed for HSP60/70 and LC3B-II. Results: WI and HS induced HSP60and HSP70, respectively. The induced HSP60/70 effectively prevented the development of cerulein-induced AP. Autophagy developed in the rats with cerulein-induced AP and was documented by the expression of LC3-II and electron microscopy fi ndings. The WI-stressed rats and HS-treated rats did not develop cerulein-induced autophagy. Conclusions: HSPs exert protective effects against cerulein-induced AP in rats by inhibiting autophagy.
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