Oxidant-induced inhibition of the plasma membrane Ca~(2+)-ATPase in pancreatic acinar cells: role of the mitochondria

摘要

The transition between apoptotic and necrotic cell death has been suggested to be one of the most important features of acute pancreatitis, regardless of the causative agent or process (6). Apoptotic cell death is a carefully controlled event that leads to the "clean" dismantling of the cellular constituents and the ultimate removal of cell remnants by phagocytosis. In this respect, apoptosis in the pancreas can be protective, although in excess it can lead to the progressive loss of pancreatic tissue (and thus function) that is the hallmark of chronic pancreatitis (6). Necrosis, on the other hand, is a more uncontrolled event that leads to the "messy" and chaotic destruction of the cell, and it is characterized by vacuole formation, blebbing, and, ultimately, cell lysis. This leads to the release of potentially damaging cellular constituents, such as activated proteases, that can damage neighboring cells, resulting in a spiral of self-perpetuating tissue damage and inflammation. The Ca~(2+) overload response has been suggested to underlie this transition between apoptosis and necrosis (47) and thus represents an important mechanism in further understanding the pathology of acute pancreatitis