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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wong, James Patel, Waseema Bruce, Jason I. E. Whitehouse, John Alves-simoes, Marta Mankad, Parini Samad, Aysha James, Andrew Siriwardena, Ajith K. |
| Description | Author Affiliation: Samad A ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); James A ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); Wong J ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); Mankad P ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); Whitehouse J ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); Patel W ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); Alves-Simoes M ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and.); Siriwardena AK ( the Hepatobiliary Surgery Unit, Manchester Royal Infirmary, M13 9WL Manchester, United Kingdom.); Bruce JI ( From the Faculty of Life Sciences, The University of Manchester, M13 9NT Manchester and jason.bruce@manchester.ac.uk.) |
| Abstract | Acute pancreatitis is a serious and sometimes fatal inflammatory disease where the pancreas digests itself. The non-oxidative ethanol metabolites palmitoleic acid (POA) and POA-ethylester (POAEE) are reported to induce pancreatitis caused by impaired mitochondrial metabolism, cytosolic $Ca^{2+}$ $([Ca^{2+}]_{i})$ overload and necrosis of pancreatic acinar cells. Metabolism and $[Ca^{2+}]_{i}$ are linked critically by the ATP-driven plasma membrane $Ca^{2+}-ATPase$ (PMCA) important for maintaining low resting $[Ca^{2+}]_{i}.$ The aim of the current study was to test the protective effects of insulin on cellular injury induced by the pancreatitis-inducing agents, ethanol, POA, and POAEE. Rat pancreatic acinar cells were isolated by collagenase digestion and $[Ca^{2+}]_{i}$ was measured by fura-2 imaging. An in situ $[Ca^{2+}]_{i}$ clearance assay was used to assess PMCA activity. Magnesium green (MgGreen) and a luciferase-based ATP kit were used to assess cellular ATP depletion. Ethanol (100 mm) and POAEE (100 μm) induced a small but irreversible $Ca^{2+}$ overload response but had no significant effect on PMCA activity. POA (50–100 μm) induced a robust $Ca^{2+}$ overload, ATP depletion, inhibited PMCA activity, and consequently induced necrosis. Insulin pretreatment (100 nm for 30 min) prevented the POA-induced $Ca^{2+}$ overload, ATP depletion, inhibition of the PMCA, and necrosis. Moreover, the insulin-mediated protection of the POA-induced $Ca^{2+}$ overload was partially prevented by the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002. These data provide the first evidence that insulin directly protects pancreatic acinar cell injury induced by bona fide pancreatitis-inducing agents, such as POA. This may have important therapeutic implications for the treatment of pancreatitis. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 34 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-08-22 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Fatty Acids, Monounsaturated Pharmacology Insulin Physiology Pancreas Drug Effects Adenosine Triphosphate Metabolism Animals Calcium Cell Death Chromones Ethanol Administration & Dosage Fatty Acids Fluorescence Morpholines Cytology Plasma Membrane Calcium-Transporting ATPases Rats, Sprague-Dawley Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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