Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heat shock or stress proteins (HSPs) are synthesized by various cell types in response to different metabolic insults (e.g., hyperthermia). Although the function of HSPs is not fully understood, they are believed to be an evolutionary conserved intracellular defense mechanism. In an attempt to characterize the autoprotective potential of pancreatic acinar cells, we investigated the regulation of HSPs of the 70-kD family and the small HSP ubiquitin in vitro and in vivo during supramaximal cerulein stimulation. Infusion of the secretagogue cerulein induces a mild edematous form of pancreatitis in vivo and is characterized by a marked disturbance of the intracellular transport and segregation of enzymes. Synthesis of HSP70 mRNA is upregulated in isolated pancreatic lobules by either cerulein (100 nM) or hyperthermia (42 degrees C for 60 min). In contrast, expression of ubiquitin mRNA was not altered by either secretagogue treatment or hyperthermia. This heat shock-like response of pancreatic acinar cells could be reproduced in vivo: Pancreatitis was induced in male Wistar rats by intravenous infusion of supramaximal doses of cerulein (10 micrograms/kg/h). Analysis of mRNA expression revealed a significant upregulation of HSP70 RNA during supramaximal secretagogue stimulation. mRNA levels encoding for ubiquitin remained unchanged. Western blot analysis demonstrated that the transcriptional upregulation of HSP70 in vivo was reflected on the protein level. This study demonstrates that the marked intracellular disturbance observed in secretagogue-induced pancreatitis is associated with enhanced expression and synthesis of a major stress protein. Given the autoprotective potential of HSPs, this upregulation may indicate a self-defense mechanism of pancreatic acinar cells in experimental pancreatitis.
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PMID:Supramaximal secretagogue stimulation enhances heat shock protein expression in the rat pancreas. 779 92

We have recently reported that preconditioning through hyperthermia induces expression of pancreatic heat shock proteins (HSPs) and protects against caerulein pancreatitis. Here, we investigate caerulein-mediated effects on pancreatic HSPs without prior hyperthermia. Caerulein time and dose dependently increased pancreatic mRNA levels of the constitutive isoform of HSP70 (HSC70). However, pancreatic HSC70 protein levels were decreased, as were HSP60 protein levels. Also, in contrast to hyperthermia preconditioning, caerulein did not induce measurable levels of mRNA or protein of the inducible isoform of HSP70. Thus the pancreas reacts to different kinds of stress (hyperthermia vs. hyperstimulation) with differential induction of HSP mRNAs. Clearly, hyperthermia leads to induction of HSP protein expression, whereas caerulein treatment does not. Therefore, our current study further supports the idea that hyperthermia-induced protection against caerulein pancreatitis may be mediated through increased protein levels of pancreatic HSPs. It is further tempting to hypothesize that failure to appropriately increase HSP protein levels in response to high doses of caerulein might be a factor in the development of pancreatitis.
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PMID:Caerulein pancreatitis increases mRNA but reduces protein levels of rat pancreatic heat shock proteins. 935 38

With the acute necrotizing pancreatitis rat model induced by giving sodium taurocholate, the expression of hsp70 gene was detected in exocrine pancreas using Northern hybridization and immunohistochemistry. Nothern hybridization analysis showed that the levels of hsp70 gene expression increased and peaked at 1 h after operation, and declined to the control levels at 8-16 h. In immunohistochemistry detection, the staining for HSP70 protein enhanced significantly at 1 h, peaked at 2 h, and then decreased, persisting for 16 h or longer. The location of the large particle positive signal for HSP70 was in the apical region of the acinar cells, while very few signals for HSP70 were observed in the basal region, nucleus and acinar lumen. The results suggest that the high expression of hsp70 gene in the acinar cells may be involved in the transportation of pancrease enzymes synthesized excessively and in the prevention of early enzyme activation.
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PMID:[The expression of HSP-70 gene in exocrine pancreas of the rats suffering from acute necrotizing pancreatitis]. 1007 14

The dually phosphorylated c-jun kinase and p38 mitogen-activated protein (MAP) kinase, also termed stress kinases, are members of the MAP kinase family. They are activated early during cerulein pancreatitis induction and have been proposed as regulators during pancreatitis development by us and others. We recently showed that hyperthermia preconditioning induces expression of pancreatic heat-shock proteins (HSP) and protects against cerulein pancreatitis. Because it was further reported that HSP70 can prevent activation of stress kinases in lymphoid tumor cells, we investigated whether hyperthermia preconditioning might reduce hyperstimulation-mediated activation of pancreatic stress kinases. Pancreatic HSP expression was induced by whole-body hyperthermia preconditioning. Without prior HSP induction, cerulein led to a rapid and dose-dependent increase in serum lipase and amylase levels, pancreatic wet weight through edema formation, and activation of pancreatic MAP kinases. Hyperthermia preconditioning, although strongly inducing HSP70 and almost completely preventing edema formation, as well as the increase of serum amylase and lipase, did not reduce cerulein-mediated stress kinase activation. This indicates that in the pancreas, cerulein can strongly activate MAP kinases even when pancreatitis development is greatly inhibited, and that pancreatic HSPs do not inhibit activation of pancreatic stress kinases in vivo.
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PMID:Hyperthermia, inducing pancreatic heat-shock proteins, fails to prevent cerulein-induced stress kinase activation. 1043 62

Rodents given a supramaximally stimulating dose of cholecystokinin or its analogue cerulein develop acute pancreatitis with acinar cell injury, pancreatic inflammation, and intrapancreatic digestive enzyme (i.e., trypsinogen) activation. Prior thermal stress is associated with heat shock protein 70 (HSP70) expression and protection against cerulein-induced pancreatitis. However, thermal stress can also induce expression of other HSPs. The current studies were performed using an in vitro system to determine whether HSP70 can actually mediate protection against pancreatitis and, if so, to define the mechanism underlying that protection. We show that in vitro exposure of freshly prepared rat pancreas fragments to a supramaximally stimulating dose of cerulein results in changes similar to those noted in cerulein-induced pancreatitis, i.e., intra-acinar cell trypsinogen activation and acinar cell injury. Short-term culture of the fragments results in HSP70 expression and loss of the pancreatitis-like changes noted after addition of cerulein. The culture-induced enhanced HSP70 expression can be prevented by addition of either the flavonoid antioxidant quercetin or an antisense oligonucleotide to HSP70. Under these latter conditions, addition of a supramaximally stimulating concentration of cerulein results in trypsinogen activation and acinar cell injury. These findings indicate that the protection against cerulein-induced pancreatitis that follows culture-induced (and possibly thermal) stress is mediated by HSP70. They suggest that the HSP acts by preventing trypsinogen activation within acinar cells.
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PMID:Heat shock protein 70 prevents secretagogue-induced cell injury in the pancreas by preventing intracellular trypsinogen activation. 1088 51

Heat shock proteins (HSPs) 70 and 27 are stress-responsive proteins that are important for cell survival after injury; the expression of these HSPs is regulated primarily by the transcription factor heat shock factor-1 (HSF-1). The purpose of this study was to determine the effect of acute pancreatitis on pancreatic HSPs (70, 27, 60, and 90) expression and to assess potential mechanisms for HSP induction using a murine model of cerulein-induced pancreatitis. We found an increase of both HSP70 and HSP27 levels with expression noted throughout the pancreas after induction of pancreatitis. HSP60 and HSP90 levels were constitutively expressed in the pancreas and did not significantly change with acute pancreatitis. HSF-1 DNA binding activity increased in accordance with increased HSP expression. We conclude that acute pancreatitis results in a marked increase in the expression of HSP70 and HSP27. Furthermore, the induction of HSP70 and HSP27 expression was associated with a concomitant increase in HSF-1 binding activity. The increased expression of both HSP70 and HSP27 noted with pancreatic inflammation may confer a protective effect for the remaining acini after acute pancreatitis.
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PMID:Acute pancreatitis results in induction of heat shock proteins 70 and 27 and heat shock factor-1. 1103 68

We recently reported that hyperthermia induces pancreatic expression of heat shock proteins (HSPs), particularly HSP70 isoforms, and protects against cerulein pancreatitis. We have now studied whether a double hyperthermia amplifies these effects and whether hyperthermia also protects against dibutyltin dichloride (DBTC)-induced pancreatitis. A further aim was to examine whether hyperthermia induces changes in transforming growth factor-beta1 (TGF-beta1). Following pretreatment without or with a single or double hyperthermia, pancreatitis was induced by application of cerulein or DBTC. Pancreatic HSP and TGF-beta1 expression were studied by immunoblotting. Pancreas injury was assessed by light microscopy and serum pancreatic enzyme activity. Hyperthermia as well as DBTC induced HSP72, whereas cerulein did not. A double hyperthermia led to a further increase in HSP72 compared to a single heat stress. In both models, hyperthermia significantly reduced pancreatic injury. Although a double hyperthermia slightly decreased the severity of cerulein pancreatitis compared to a single heat treatment, an improved pancreas protection against DBTC cytotoxicity was not achieved. We also found that hyperthermia induces the expression of TGF-beta1. In conclusion, hyperthermia preconditioning exerts protective effects against two pathophysiologically different types of pancreatitis by a mechanism that involves the up-regulation of HSP70 isoforms as well as TGF-beta1.
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PMID:Heat shock response is associated with protection against acute interstitial pancreatitis in rats. 1121 49

Arginine induced acute pancreatitis was evaluated as a novel and distinct form of experimental pancreatitis with particular attention to the actin cytoskeleton and expression of heat shock or stress proteins. Arginine induced a dose related necrotising pancreatitis in rats, as shown by histological evaluation, and an increase in serum amylase. Severe pancreatitis induced by 4.5 g/kg arginine was accompanied by dramatic changes in the actin cytoskeleton, as visualised with rhodamine phallodin. Intermediate filaments were also disrupted, as visualised by cytokeratin 8/18 immunocytochemistry. Arginine pancreatitis was accompanied by a stress response with a large increase in the small heat shock protein HSP27, as well as HSP70, peaking at 24 hours and localised to acinar cells. There was a lower increase in HSP60 and HSP90 and no effect on GRP78. HSP27 was also shifted to phosphorylated forms during pancreatitis. A lower dose of arginine (3.0 g/kg) induced less pancreatitis but a larger increase in HSP70 and HSP27 expression and phosphorylation of HSP27. Thus HSP expression can be overwhelmed by severe damage. The present work in conjunction with earlier work on caerulein induced pancreatitis indicates that changes in the actin cytoskeleton are an early component in experimental pancreatitis.
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PMID:Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cells. 1145 2

Heat shock proteins (HSPs) which are induced by stress can provide protection against subsequent cellular damage. Whole body hyperthermia in rats leading to induction of HSP70 has been shown to protect against subsequent caerulein-induced acute pancreatitis. We studied the effect of hyperthermia on pancreatic HSP expression and found a significant increase in HSP70 (26.0-fold) and HPS27 (6.0-fold) but no change in HSP60, HSP90 or GRP78. Hyperthermia conferred significant protection against subsequent arginine-induced acute pancreatitis. More specifically, the degradation and disorganization of the actin cytoskeleton, an important early component of acute pancreatitis, was prevented. These results generalize previous work on caerulein-induced pancreatitis to another model of experimental pancreatitis, arginine-induced pancreatitis, and suggest that multiple HSPs may be involved in the cytoprotective effect in rat pancreas.
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PMID:Hyperthermia induces multiple pancreatic heat shock proteins and protects against subsequent arginine-induced acute pancreatitis in rats. 1202 85

It has been widely shown that preconditioning, inducing heat shock proteins, can protect against experimentally induced pancreatitis. Solid evidence indicates that HSP70 plays a central role in this context, possibly by inhibition of premature intracellular trypsinogen activation. Current preconditioning protocols such as whole body hyperthermia are, however, quite strenuous and clinically not applicable. There is little data on other means to induce pancreatic HSPs such as pharmacologic pretreatment.However, in models of ischemic liver reperfusion injury, it has been demonstrated that atrial natriuretic peptide (ANP) can be used for such pharmacologic preconditioning. Evidence indicates that ANP exerts its protective effects via increased cGMP levels, activation of heat shock transcription factor (HSF) and, increased protein levels of HSP70. Pancreatic acinar cells express ANP receptors and respond to ANP treatment with increased cGMP levels. We have, therefore, investigated whether intravenous ANP pretreatment could be used to protect the pancreas against experimental pancreatitis. When given 20 minutes prior to pancreatitis induction, ANP pretreatment had no effect on cerulein-induced pancreatitis. In contrast, 24 hours after preconditioning, induction of HSP70 protein expression and protection against experimental pancreatitis were found. However, controls treated with NaCl without ANP showed a similar response. This indicates that stress caused by general anesthesia and jugular vein catheterization can be sufficient for preconditioning while ANP, in contrast to models of ischemic liver reperfusion injury, does not confer additional protection.
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PMID:ANP preconditioning does not increase protection against experimental pancreatitis, observed after general anesthesia and jugular vein catheterization. 1502 49


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