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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A membrane-bound system through which secretory and lysosomal proteins travel in a vectorial fashion is essential for the preserved integrity of pancreatic acinar cells. This system is composed of an ordered array of compartments, such as the rough endoplasmic reticulum, the Golgi complex, lysosomes, and secretory granules. As a principle, in acute pancreatitis the final steps of this transport seem to be disturbed. Caerulein-induced pancreatitis is a valuable experimental model for studying altered intracellular transport, and compartmentation of lysosomal and digestive enzymes. The formation of enlarged secretory vacuoles containing lysosomal and digestive enzymes is paralleled by the activation of lysosomes and degradation of cellular organelles in autophagosomes. On the level of secretory and autophagic vacuoles, activation of serine proteases occurs, which in addition to increasing lysosomal enzyme activities can represent the initial stage for acinar cell destruction and the development of pancreatitis.
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PMID:Mechanism of acute pancreatitis. Cellular and subcellular events. 174 43

The complex events by which digestive enzyme zymogens and lysosomal hydrolases are segregated from each other and differentially transported to their respective membrane-bound intracellular organelles in the pancreas have been noted to be disturbed during the early stages of several models of experimental pancreatitis. As a result, lysosomal hydrolases such as cathepsin B are redistributed to the subcellular zymogen granule-rich fraction and lysosomal hydrolases as well as digestive enzyme zymogens are colocalized within large cytoplasmic vacuoles. The current study was designed to create an in vitro system that would reproduce this redistribution phenomenon. Our results indicate that cathepsin B redistribution occurs when rat pancreatic fragments are incubated with a supramaximally stimulating concentration of the cholecystokinin analogue caerulein along with plasma from an animal subjected to in vivo supramaximal caerulein stimulation. Neither the plasma nor a supramaximally stimulating concentration of caerulein, alone, is sufficient to induce in vitro cathepsin B redistribution. The ability of the plasma to induce in vitro cathepsin redistribution is dependent upon its content of a 10,000-30,000-D protein and is lost by exposure to protease inhibitors. In vitro cathepsin B redistribution also occurs when rat pancreatic fragments are incubated with plasma obtained from opossums with hemorrhagic necrotizing pancreatitis caused by bile/pancreatic duct ligation.
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PMID:A plasma protease which is expressed during supramaximal stimulation causes in vitro subcellular redistribution of lysosomal enzymes in rat exocrine pancreas. 201 May 41

Caerulein-induced acute pancreatitis is characterized by the occurrence of two membrane-bound vacuolar systems in acinar cells. Beside digestive enzymes containing secretory vacuoles, lysosomal autophagic structures can be identified at the ultrastructural level. In the present study glycoconjugate patterns of the surrounding membranes were characterized by ultrastructural lectin-binding experiments using five colloidal-gold labeled lectins with distinct sugar specificities. Furthermore, the profile of membrane glycoproteins of isolated vacuolar fractions was studied by SDS-PAGE and lectin-blotting. In pancreatitis, membranes of secretory vacuoles showed a significant lower degree of lectin-binding compared to normal zymogen granules. In contrast, newly appearing autophagic vacuoles in pancreatitis revealed a strong membrane labelling for most lectins used. The pattern of membrane glycoproteins of secretory and autophagic vacuoles as determined by SDS-PAGE and lectin-blotting differed from those of normal zymogen granules resembling the protein profile of smooth microsomes. Since this pattern requires a previous passage through Golgi stacks, it is assumed that the two types of vacuoles derive from Golgi elements. For the pathogenesis of caerulein pancreatitis these vacuolar post-Golgi structures seem to play an important role.
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PMID:Caerulein-induced acute pancreatitis in rats: changes in glycoprotein-composition of subcellular membrane systems in acinar cells. 228 36

To study the regulation of the successive steps along the secretory pathway in the rat exocrine pancreas the model of in vivo infusion of synthetic caerulein in conscious rats for periods up to 72 h was combined with electron microscopy and in vitro analysis of protein synthesis, intracellular protein transport and enzyme discharge using isolated pancreatic lobules. Prolonged and maximal hormonal stimulation was obtained with 0.25 microgram kg-1 h-1 caerulein and resulted in a 80-90% depletion of enzyme stores within 1 to 3 h, followed by coordinate and anticoordinate changes in individual rates of (pro-)enzyme synthesis after a lag period of 3 h. One group (two amylases) revealed a decrease in synthesis to levels about 10-fold lower than controls. A third group of proteins (one trypsinogen, lipase, proelastase) did not show changes in synthesis with hormone stimulation. The sum of such alterations led to an increase in total rate of synthesis after 6 h, which was combined with acceleration of intracellular transport, packaging, and granule discharge, thus enabling a sustained rate of secretion over the period of stimulation. In contrast, infusion of a supramaximal dose of caerulein (5.0 micrograms kg-1 h-1) induced acute edematous pancreatitis and led to an almost complete reduction of volume and protein output from the cannulated main pancreatic duct. Using freeze-fracture techniques and thin-section electron microscopy, earliest structural alterations were observed at membranes of zymogen granules and the plasma membrane. Fusion of zymogen granules among each other led to formation of large membrane-bound vacuoles within the cytoplasm. These and individual zymogen granules fused with the lateral instead of the apical plasma membrane, discharging their content into the interstitial space. Vacuole formation was associated with activation of lysosomes and with cytoplasmic destruction of acinar cells. The findings indicated severe changes in the specificity of the intracellular membrane fusion process induced by supramaximal doses of caerulein, which finally resulted in autodigestion of the pancreas.
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PMID:Structural and biochemical characterization of maximal and supramaximal hormonal stimulation of rat exocrine pancreas. 385 14

Infusion of supramaximal doses of cerulein induces acute edematous pancreatitis in the rat. Cannulation of the main pancreatic duct does not prevent the formation of the edema but reveals an almost complete reduction of pancreatic flow. Using freeze-fracture techniques and thin-section electron microscopy, earliest structural alterations were observed at membranes of zymogen granules and the plasma membrane. Fusion of zymogen granules among each other leads to formation of large membrane-bound vacuoles within the cytoplasm. These and individual zymogen granules fuse with the basolateral plasma membrane, discharging their content into the interstitial space. The findings indicate severe changes in the specificity of the intracellular membrane fusion process induced by supramaximal doses of a pancreatic secretagogue, which finally result in autodigestion of the pancreas.
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PMID:Alteration of membrane fusion as a cause of acute pancreatitis in the rat. 714 Apr 96

Among more than ten isozymes of the carbonic anhydrase (CA) family, only cytoplasmic CA II and membrane-bound CA IX have been reported to be expressed in human pancreas. To study the mRNA expression of CA isozymes in human pancreas, reverse transcriptase-polymerase chain reaction (RT-PCR)-Southern blot analysis and cDNA sequencing following RT-PCR were employed. CA II, IV, VI, IX, and XII were clearly identified in polyA+ RNA from normal human pancreas by RT-PCR-Southern blotting. Results with cultured pancreatic tumor cell, lines suggest that CA II, IV, IX, and XII are expressed in the ductal cells, and CA VI is expressed in the acinar cells. We propose a hypothesis for the pathophysiological function of CA isozymes in human pancreas; (1) the intraluminal CA isozymes (CA IV, VI, and possibly XII) form a mutually complementary system with cytoplasmic CA II to regulate the luminal pH of the pancreatic duct system and work as a self-defense mechanism against pancreatitis; (2) CA II and other CA isozymes play a pathological role in the autoimmune process of idiopathic chronic pancreatitis.
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PMID:Carbonic anhydrase in human pancreas: hypotheses for the pathophysiological roles of CA isozymes. 1041 46

Severe acute pancreatitis (SAP) can cause intestinal barrier dysfunction (IBD), which significantly increases the disease severity and risk of mortality. We hypothesized that the innate immunity- and inflammatory-related protein-triggering receptor expressed on myeloid cells-1 (TREM-1) contributes to this complication of SAP. Thus, we investigated the effect of TREM-1 pathway modulation on a rat model of pancreatitis-associated IBD. In this study we sought to clarify the role of TREM-1 in the pathophysiology of intestinal barrier dysfunction in SAP. Specifically, we evaluated levels of serum TREM-1 and membrane-bound TREM-1 in the intestine and pancreas from an animal model of experimentally induced SAP. TREM-1 pathway blockade by LP17 treatment may suppress pancreatitis-associated IBD and ameliorate the damage to the intestinal mucosa barrier.
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PMID:TREM-1 Promotes Pancreatitis-Associated Intestinal Barrier Dysfunction. 2261 79

Pathophysiology of acute pancreatitis (AP) has not been clearly established; nevertheless, accumulating evidence implicates highly reactive oxygen species (ROS) as important mediators of exocrine tissue damage. In this study, we used a water-soluble radical initiator, 2,2 -azobis-(2-amidinopropane) dihydrochloride (AAPH), to investigate the consequences of oxidative stress insult to the rat pancreas. The detailed characterisation of acini ultrastructural changes in the early course (3, 6, 12, 24 h) of AAPH-induced pancreatitis (40 mg/1 kg body weight) was performed. Considerable damage to the mitochondria in acinar cells manifested by increased translucence of the matrix, partial destruction of cristae, and formation of myelin figures were noted. At the same time, focal dilation, degranulation of rough endoplasmic reticulum, and reduced number of zymogen granules was observed. The most prominent ultrastructural feature was accumulation of highly polymorphic cytoplasmic vacuoles in acinar cells. Double membrane-bound autophagosomes, different in size and shape, with sequestered organelles, autophagolysosomes, and large, empty, single-membrane-bound vacuoles were observed within the cytoplasm. The results indicate that intensive and impaired autophagy mediates pathological accumulation of vacuoles in acinar cells. The rat model of acute pancreatitis induced by AAPH is useful to investigate the early events of oxidative stress insult to the pancreas.
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PMID:Ultrastructural aspects of acute pancreatitis induced by 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in rats. 2293 47