Which Way to Die: the Regulation of Acinar Cell Death in Pancreatitis by Mitochondria, Calcium, and Reactive Oxygen Species

Abstract

Acute pancreatitis is an inflammatory disorder of exocrine pancreas, which carries considerable morbidity and mortality; its pathophysiology remains elusive.1 During the past decade, significant progress has been achieved in our understanding of the inflammatory response in pancreatitis.1 Much less is known about the mechanisms mediating another key pathologic response of pancreatitis, namely acinar cell death. In human disease and experimental pancreatitis, acinar cells die through both apoptosis and necrosis. These 2 main types of cell death differ morphologically and biochemically.2,3 Key molecular steps in the apoptotic pathway are the release of cytochrome c from mitochondria and activation of caspases, a specific class of cysteine proteases. Importantly, apoptosis preserves the plasma membrane integrity, whereas necrotic cell releases its constituents, damaging neighboring cells and promoting inflammation. Therefore, necrotic death is “deadlier” to the organism than apoptotic death.2,3