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Preparation of Pancreatic Acinar Cells for the Purpose of Calcium Imaging, Cell Injury Measurements, and Adenoviral Infection
Published on: July 5, 2013
Vacuolar adenosine triphosphatase and pancreatic acinar cell function
Fred S Gorelick1, Christine A Shugrue, Thomas R Kolodecik
1Department of Internal Medicine, Connecticut VA Healthcare, West Haven, CT 06516, USA. fred.gorelick@yale.edu
Journal of Gastroenterology and Hepatology
|September 9, 2006
Summary
Vacuolar adenosine triphosphatase (vATPase) activation is central to pancreatic acinar cell injury in acute pancreatitis. Inhibiting vATPase blocks protease activation and alcohol-induced sensitization, suggesting therapeutic potential.
Area of Science:
- Cell Biology
- Gastroenterology
- Biochemistry
Background:
- Pathologic activation of proteases in pancreatic acinar cells initiates acute pancreatitis.
- A low-pH environment is critical for this protease activation.
- Vacuolar adenosine triphosphatase (vATPase) regulates proton transport across cellular membranes.
Purpose of the Study:
- To investigate the role of vATPase in the activation of pancreatic proteases.
- To determine if vATPase activation is involved in alcohol-induced sensitization of pancreatic acinar cells.
Main Methods:
- Studied the assembly of vATPase subunits (V(1) and V(0)) under conditions causing protease activation.
- Utilized vATPase inhibitors to block protease activation and alcohol-induced sensitization.
- Examined the effects of ethanol and butanol on cholecystokinin-induced zymogen activation.
Main Results:
- Conditions causing protease activation also induced the assembly of V(1) on V(0) subunits of vATPase.
- vATPase inhibitors effectively blocked protease activation in pancreatic acinar cells.
- vATPase inhibitors prevented the sensitizing effects of ethanol and butanol on zymogen activation.
Conclusions:
- vATPase activation is a key event in the pathologic activation of proteases within pancreatic acinar cells.
- vATPase plays a role in modulating the sensitizing effects of alcohols on the pancreas.
- Targeting vATPase may offer a therapeutic strategy for acute pancreatitis.
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