摘要
Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca<sup>2+</sup>) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca<sup>2+</sup> overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca<sup>2+</sup> signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca<sup>2+</sup> elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca<sup>2+</sup> from stores in the intracellular endoplasmic reticulum and/or increased Ca<sup>2+</sup> entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca<sup>2+</sup> by the sarco/endoplasmic reticulum Ca<sup>2+</sup>-activated ATPase and plasma membrane Ca<sup>2+</sup>-ATPase pumps, which contribute to Ca<sup>2+</sup> overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca<sup>2+</sup> signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca<sup>2+</sup> signals in the pathogenesis of pancreatitis.
Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy.The pathogenesis of pancreatitis is still not well understood.Calcium(Ca2+)is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells.Ca2+overload is a key early event and is crucial in the pathogenesis of many diseases.In pancreatic acinar cells,pathological Ca2+signaling(stimulated by bile,alcohol metabolites and othercauses)is a key contributor to the initiation of cell injury due to prolonged and global Ca2+elevation that results in trypsin activation,vacuolization and necrosis,all of which are crucial in the development of pancreatitis.Increased release of Ca2+from stores in the intracellular endoplasmic reticulum and/or increased Ca2+entry through the plasma membrane are causes of such cell damage.Failed mitochondrial adenosine triphosphate(ATP)production reduces re-uptake and extrusion of Ca2+by the sarco/endoplasmic reticulum Ca2+-activated ATPase and plasma membrane Ca2+-ATPase pumps,which contribute to Ca2+overload.Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca2+signals in pancreatitis.The lack of available specific treatments is therefore an objective of ongoing research.Research is currently underway to establish the mechanisms and interactions of Ca2+signals in the pathogenesis of pancreatitis.
基金
Supported by grants from the National Natural Science Foundation of China No.30171167,No.30901945
the Specialized Research Fund for the Doctoral Program of Higher Education No.20130201130009
