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Sci. STKE, 27 July 2004
Vol. 2004, Issue 243, p. tw273
[DOI: 10.1126/stke.2432004tw273]

EDITORS' CHOICE

PANCREATIC NECROSIS Intoxicating Fatty Acids

Ethanol excess can cause severe pancreatic injury, such as acute pancreatitis. Organ necrosis, eventual failure, and even death may occur. Criddle et al. report that ethanol itself may not be the major culprit of pancreatic necrosis, but rather a fatty acid ethyl ester (FAEE) metabolite of ethanol. Exposure of cultured pancreatic acinar cells to the nonoxidative FAEE metabolite palmitoleic acid ethyl ester (POAEE) caused a sustained, global increase in intracellular calcium. The rise in calcium activates intracellular digestive enzymes and vacuolization that mark the early stages of pancreatic cell injury. Even at 850 mM, ethanol generally caused only a transient increase in intracellular calcium. In contrast, treatment of cells with POAEE (from 10 μM to 100 μM) resulted in a global, sustained increase in intracellular calcium and cell necrosis. A pharmacological inhibitor indicated that calcium was released from intracellular stores. However, the absence of extracellular calcium blocked a rise in intracellular calcium in response to low concentrations of POA (a deesterification product), which implicated a store-operated calcium entry channel in generating the calcium signal. When people are intoxicated, FAEE concentration in their blood may reach as high as 50 μM, and its accumulation is highest in the pancreas.

D. N. Criddle, M. G. T. Raraty, J. P. Neoptolemos, A. V. Tepikin, O. H. Petersen, R. Sutton, Ethanol toxicity in pancreatic acinar cells: Mediation by nonoxidative fatty acid metabolites. Proc. Natl. Acad. Sci. U.S.A. 101, 10738-10743 (2004). [Abstract] [Full Text]

Citation: Intoxicating Fatty Acids. Sci. STKE 2004, tw273 (2004).



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