OBJECTIVES: Alcohol abuse is a major cause of pancreatitis, which is associated with death of parenchymal cells. The goal of this study was to explore the effects of ethanol on cell death pathways in the pancreas. METHODS: Adult male Wistar rats were fed with ethanol diets using the Lieber-DeCarli method. Caspase-8, caspase-3, and cathepsin B expression and activity in the pancreas of these animals as well as the signals that regulate their expression were studied using Western blot analysis and specific assays for biochemical enzyme activity. RESULTS: In the pancreas from rats fed with ethanol, the protein expression and activity of caspase-8 decreased by 48% and 45%, respectively, and caspase-3 activity decreased by 39%. In contrast, cathepsin B protein expression and activity increased with ethanol feeding by 189% and 143%, respectively. Evaluation of the transcriptional regulatory system for caspase-8 and cathepsin B showed that the ethanol effects on these pathways were largely transcriptional. CONCLUSIONS: Our findings show effects of ethanol on the expression of several signals involved in cell death in the pancreas through alteration of transcriptional regulators. The decrease in caspase expression and increase in cathepsin B expression indicate that ethanol feeding may prevent apoptosis and promote necrosis of pancreatic tissue with stresses that cause pancreatitis.
OBJECTIVES:Alcohol abuse is a major cause of pancreatitis, which is associated with death of parenchymal cells. The goal of this study was to explore the effects of ethanol on cell death pathways in the pancreas. METHODS: Adult male Wistar rats were fed with ethanol diets using the Lieber-DeCarli method. Caspase-8, caspase-3, and cathepsin B expression and activity in the pancreas of these animals as well as the signals that regulate their expression were studied using Western blot analysis and specific assays for biochemical enzyme activity. RESULTS: In the pancreas from rats fed with ethanol, the protein expression and activity of caspase-8 decreased by 48% and 45%, respectively, and caspase-3 activity decreased by 39%. In contrast, cathepsin B protein expression and activity increased with ethanol feeding by 189% and 143%, respectively. Evaluation of the transcriptional regulatory system for caspase-8 and cathepsin B showed that the ethanol effects on these pathways were largely transcriptional. CONCLUSIONS: Our findings show effects of ethanol on the expression of several signals involved in cell death in the pancreas through alteration of transcriptional regulators. The decrease in caspase expression and increase in cathepsin B expression indicate that ethanol feeding may prevent apoptosis and promote necrosis of pancreatic tissue with stresses that cause pancreatitis.
Authors: Stephen J Pandol; Aurelia Lugea; Olga A Mareninova; Duane Smoot; Fred S Gorelick; Anna S Gukovskaya; Ilya Gukovsky Journal: Alcohol Clin Exp Res Date: 2011-02-01 Impact factor: 3.455
Authors: Bhupendra S Kaphalia; Kamlesh K Bhopale; Shakuntala Kondraganti; Hai Wu; Paul J Boor; G A Shakeel Ansari Journal: Toxicol Appl Pharmacol Date: 2010-05-15 Impact factor: 4.219
Authors: Aurelia Lugea; Jun Gong; Janie Nguyen; Jose Nieto; Samuel W French; Stephen J Pandol Journal: Alcohol Clin Exp Res Date: 2010-07-09 Impact factor: 3.455
Authors: Samir M Amer; Kamlesh K Bhopale; Ramu D Kakumanu; Vsevolod L Popov; Bill A Rampy; Inas H El-Mehallawi; Magdy M Ashmawy; G A Shakeel Ansari; Bhupendra S Kaphalia Journal: Exp Mol Pathol Date: 2018-01-11 Impact factor: 3.362