Expression differences in mitochondrial and secretory chaperonin 60 (Cpn60) in pancreatic acinar cells

Abstract

In pancreatic acinar cells, chaperonin Cpn60 is present in all the cellular compartments involved in protein secretion as well as in mitochondria. To better understand the role Cpn60 plays in pancreatic secretion, we have evaluated its changes under experimental conditions known to alter pancreatic secretion. Quantitative protein A-gold immunocytochemistry was used to reveal Cpn60 in pancreatic acinar cells. Cpn60 immunolabelings in cellular compartments involved in secretion were found to decrease in acute pancreatitis as well as upon stimulation of secretion and in starvation conditions. A major increase in Cpn60 was recorded in diabetic condition. This was normalized by insulin treatment. Although in certain situations changes in secretory enzymes and in Cpn60 correlate well, in others, nonparallel secretion seemed to take place. In contrast, expression of mitochondrial Cpn60 in acinar cells appeared to remain stable in all conditions except starvation, where its levels decreased. Expression of Cpn60 in the secretory pathway and in mitochondria thus appears to behave differently, and Cpn60 in the secretory pathway must be important for quality control and integrity of secretion.

Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis

“…Later, Rakonczay et al (22) confirmed that cold-water immersion could significantly increase the expression of HSP60 and partly enabled rats to resist hemorrhage-necrotizing pancreatitis induced by sodium taurocholate. Previous experiments suggested that expression of pancreatic HSP60 significantly decreased in severe acute pancreatitis, whereas trypsin and lipase levels remained at a relatively high level (18). Moreover, the expression of HSP60 decreased at 1 h but increased significantly at 5 h after the induction of mild acute pancreatitis, whereas the expression of HSP60 subsided sharply followed a brief boost in severe acute pancreatitis and the pathological changes deteriorated (16,17).…”

“…It has been found that cellular organelles like mitochondria in acinar cells express HSP60 (5,13). Along the synthesis and secretory pathway of pancreatic enzymes in acinar cells, there is an intimate coincidence of HSP60 with pancreatic lipase, amylase, and trypsin confirmed by immunoprecipitation assays; i.e., when HSP60 antibody is added to the isolated zymogen granule extracts, coprecipitation of HSP60 with digestive enzymes occurs (13,18). So far, little is known about the exact role of HSP60 during acute experimental pancreatitis in mice.…”

Alteration of Cpn60 expression in pancreatic tissue of rats with acute pancreatitis

“…It not only exists in the mitochondria of pancreatic acinar cells, but also presents in the rough endoplasmic reticulum (RER), in Golgi body (G), in zymogen granules (ZG), and in the secretory pathway of pancreatic enzymes in acinar cells (Li et al 2003;Cechetto et al 2000). It is thought that Cpn60 residing in the mitochondria plays a different role from that of the protein located in the RER-G-ZG Keskin et al 2002).…”

“…It is thought that Cpn60 residing in the mitochondria plays a different role from that of the protein located in the RER-G-ZG Keskin et al 2002). Studies have found that along the secretory pathway, there is a quantitative correlation between Cpn60 and pancreatic enzymes such as lipase, amylase, and trypsin (Bruneau et al 2000;Li et al 2003).…”

“…In our earlier work, we found that in the severe acute pancreatitis (SAP) rat model induced by retrograde injection of sodium deoxycholate into the pancreatic duct, the amount of Cpn60 protein was significantly lower in the RER, Golgi, and ZG of pancreatic acinar cells at 5 h after SAP replication, while the levels of pancreatic chymotrypsin and lipase remained high. We hypothesized that Cpn60 may have an important protective function during the AP process, and the resultant imbalance between the pancreatic enzymes and Cpn60 may play a role in the intracellular activation of the enzymes and digestive damage of pancreatic tissues (Li et al 2003;Li and Bendayan 2005). These fresh but controversial results have prompted interest in further studies on the relationship between Cpn60 expression and AP onset and development.…”