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)

We previously reported that water-immersion stress specifically induced the synthesis of a 60-kDa heat-shock protein (HSP60, chaperonin homolog) in pancreatic cells and preinduction of HSP60 completely prevented development of cerulein-induced pancreatitis in the rat in an HSP60 quantitatively dependent manner. In order to study the cytoprotective function of a 72-kDa heat-shock protein (HSP72, stress-inducible hsp70), the effect of specific preinduction of HSP72 by hyperthermia on cerulein-induced pancreatitis was investigated and compared with the effect of preinduction of HSP60 in this study. Expression of HSP60 and HSP72 in the pancreas was investigated by immunoblot before and after water immersion or hyperthermia. Following pretreatment with water-immersion stress or hyperthermia, the rats were injected with cerulein (40 micrograms/kg, intraperitoneally). The pancreas wet weight and serum amylase concentration were measured before and after cerulein injection. Hyperthermia (42.5 degrees C, 20 min) specifically induced HSP72 in the pancreas. The synthesis of HSP60 was specifically induced by water-immersion stress in the pancreas. Cerulein-induced pancreatitis was clearly prevented by specific preinduction of HSP60 by water-immersion stress. However, preinduction of HSP72 by hyperthermia had no preventive effect on cerulein-induced pancreatitis. Our findings suggest that HSP60 and HSP72 have distinct functions in the pancreas, and their induction mechanisms are also different in vivo. These results could be important for understanding the mechanism of "adaptive cytoprotection" in the pancreas mediated by heat-shock proteins.
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PMID:Differential induction of HSP60 and HSP72 by different stress situations in rats. Correlation with cerulein-induced pancreatitis. 924 49

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

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

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) are cytoprotective proteins that are expressed constitutively and/or at elevated levels upon the exposure of cells to stress. The aim of this study was to investigate the potential effects of HSP preinduction by cold- (CWI) or hot-water immersion (HWI) on pro-inflammatory cytokine production (IL-1, IL-6, TNF-alpha) in cholecystokinin-octapeptide(CCK)-induced acute pancreatitis. Rats were injected with 3 x 75 microg/kg CCK subcutaneously at intervals of 2 h at the peak level of HSP synthesis, as determined by Western blot analysis. The animals were killed by exsanguination through the abdominal aorta 2 h after the last CCK injection. The serum IL-1, IL-6, TNF-alpha, and amylase levels, the pancreatic weight/body weight ratio, and the pancreatic contents of DNA, protein, amylase, lipase and trypsinogen were measured; biopsy for histology was taken. HWI significantly elevated the HSP72 expression, while CWI significantly increased the HSP60 expression. HWI pretreatment decreased all of the measured serum cytokine levels in this acute pancreatitis model. CWI and HWI pretreatment ameliorated most of the examined laboratory and morphological parameters of CCK-induced pancreatitis. The findings suggest the possible roles of HSP60 and HSP72 in the protection against CCK-induced pancreatitis. HSP72 might also participate in the reduction of pro-inflammatory cytokine synthesis.
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PMID:Water immersion pretreatment decreases pro-inflammatory cytokine production in cholecystokinin-octapeptide-induced acute pancreatitis in rats: possible role of HSP72. 1171 68

Cells respond to stress by upregulating the synthesis of cytoprotective heat shock proteins (HSPs) and antioxidant enzymes. The aim of this study was to compare the effects of cold (CWI) or hot water immersion (HWI) stress on three different acute pancreatitis models (cholecystokinin octapeptide (CCK), sodium taurocholate (TC), and L-arginine (Arg)). We examined the levels of pancreatic HSP60, HSP72, and antioxidants after the water immersion stress. Male Wistar rats were injected with CCK, TC, or Arg at the peak level of pancreatic HSP synthesis, as determined by Western blot analysis. HWI significantly elevated HSP72 expression and CWI significantly increased HSP60 expression in the pancreas. Water immersion stress decreased the levels of pancreatic antioxidants. CWI and-HWI pretreatment ameliorated most of the examined laboratory and morphological parameters of CCK-induced pancreatitis. CWI pretreatment decreased pancreatic edema and the serum amylase level; however, the morphological damage was more severe in TC-induced acute pancreatitis. Overall, CWI and HWI pretreatment only decreased the serum cytokine concentrations in Arg-induced pancreatitis. CWI and HWI resulted in differential induction of pancreatic HSP60 and HSP72 and the depletion of antioxidants. The findings suggest the possible roles of HSP60 and (or) HSP72 (but not that of the antioxidant enzymes) in the protection against CCK- and TC-induced acute pancreatitis. Unexpectedly, CWI pretreatment was detrimental to the morphological parameters of TC-induced pancreatitis. It was demonstrated that CWI and HWI pretreatment only influenced cytokine synthesis in Arg-induced pancreatitis.
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PMID:Comparative effects of water immersion pretreatment on three different acute pancreatitis models in rats. 1199 31

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

Heat shock proteins (HSPs) are necessary in the synthesis, degradation, folding, transport, and translocation of different proteins. It is well known that the increased expression of HSPs may have a protective effect against cerulein-induced pancreatitis in rats or against choline-deficient ethionine-supplemented diet model pancreatitis in mice. The aim of this study was to investigate the potential effects of HSP preinduction by cold or hot water immersion on trypsin-induced acute pancreatitis in rats. Trypsin was injected into the interlobular tissue of the duodenal part of the pancreas at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were sacrificed by exsanguination through the abdominal aorta 6 h after the trypsin injection. The serum amylase activity, the tumor necrosis factor-alpha, interleukin-1, and interleukin-6 levels, the pancreatic weight/body weight ratio, and the pancreatic contents of DNA, protein, amylase, lipase, and trypsinogen were measured. A biopsy for histology was taken. Hot water immersion significantly elevated the HSP72 expression, while cold water immersion significantly increased the HSP60 expression. Cold water immersion pretreatment ameliorated the pancreatic edema in trypsin-induced pancreatitis, however this was not due to the HSP60. Hot water immersion pretreatment did not have any effect on the measured parameters in trypsin-induced pancreatitis. The findings suggest that the induction of HSP60 or HSP72 are not enough to protect rats against the early phase of this localized necrohemorrhagic pancreatitis model.
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PMID:Induction of heat shock proteins fails to produce protection against trypsin-induced acute pancreatitis in rats. 1214 32

A number of investigators have demonstrated that the preinduction of heat-shock protein (HSP) expression (particularly HSP60 and HSP72) by hyper- or hypothermia may have a protective effect against cerulein-induced acute pancreatitis. The aim of the present study was to induce HSPs in the pancreas and lungs by thermal (hot-water immersion, HWI) and nonthermal methods (injection of sodium arsenite intraperitoneally) and to investigate the potential effects of HSP preinduction on cholecystokinin-octapeptide (CCK) induced acute pancreatitis and pancreatitis-associated lung injury in rats. The dose-response and time-effect curves observed following HWI and sodium arsenite treatments were evaluated. Animals were injected with 3 x 75 microg/kg CCK subcutaneously at intervals of 2 hr at the peak level of HSP synthesis, as determined by Western blot analysis. The rats were killed by exsanguination through the abdominal aorta 2 or 6 hr after the last CCK injection. HWI and the injection of sodium arsenite significantly elevated the expression of HSP72 in the pancreas and lungs, whereas they did not influence the levels of HSP60. Overall, HWI pretreatment had a protective effect against CCK-induced pancreatitis and pancreatitis-associated lung injury. In contrast, the nonthermal preinduction of HSP72 by sodium arsenite did not result in any beneficial effects on the measured parameters of the disease. The findings suggest that the preinduction of HSP72 is not sufficient to protect against CCK-induced acute pancreatitis and pancreatitis-associated lung injury or that the beneficial effect of hyperthermia may not be exclusively related to HSP72 expression.
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PMID:Induction of HSP72 by sodium arsenite fails to protect against cholecystokinin-octapeptide-induced acute pancreatitis in rats. 1214 22

Insulin-dependent (type 1) diabetes mellitus (T1D) onset is mediated by individual human genetics as well as undefined environmental influences such as viral infections. The group B coxsackieviruses (CVB) are commonly named as putative T1D-inducing agents. We studied CVB replication in nonobese diabetic (NOD) mice to assess how infection by diverse CVB strains affected T1D incidence in a model of human T1D. Inoculation of 4- or 8-week-old NOD mice with any of nine different CVB strains significantly reduced the incidence of T1D by 2- to 10-fold over a 10-month period relative to T1D incidences in mock-infected control mice. Greater protection was conferred by more-pathogenic CVB strains relative to less-virulent or avirulent strains. Two CVB3 strains were employed to further explore the relationship of CVB virulence phenotypes to T1D onset and incidence: a pathogenic strain (CVB3/M) and a nonvirulent strain (CVB3/GA). CVB3/M replicated to four- to fivefold-higher titers than CVB3/GA in the pancreas and induced widespread pancreatitis, whereas CVB3/GA induced no pancreatitis. Apoptotic nuclei were detected by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay in CVB3/M-infected pancreata but not in CVB3/GA-infected pancreata. In situ hybridization detected CVB3 RNA in acinar tissue but not in pancreatic islets. Although islets demonstrated inflammatory infiltrates in CVB3-protected mice, insulin remained detectable by immunohistochemistry in these islets but not in those from diabetic mice. Enzyme-linked immunosorbent assay-based examination of murine sera for immunoglobulin G1 (IgG1) and IgG2a immunoreactivity against diabetic autoantigens insulin and HSP60 revealed no statistically significant relationship between CVB3-protected mice or diabetic mice and specific autoimmunity. However, when pooled sera from CVB3/M-protected mice were used to probe a Western blot of pancreatic proteins, numerous proteins were detected, whereas only one band was detected by sera from CVB3/GA-protected mice. No proteins were detected by sera from diabetic or normal mice. Cumulatively, these data do not support the hypothesis that CVB are causative agents of T1D. To the contrary, CVB infections provide significant protection from T1D onset in NOD mice. Possible mechanisms by which this virus-induced protection may occur are discussed.
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PMID:Toward testing the hypothesis that group B coxsackieviruses (CVB) trigger insulin-dependent diabetes: inoculating nonobese diabetic mice with CVB markedly lowers diabetes incidence. 1241 51


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