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)

Inhibition of pancreatic digestive enzyme secretion in the acinar cell is a significant phenomenon which can trigger acute pancreatitis. It has been shown that microtubules are responsible for the intracellular vesicular transport. The effect of taxol, a microtubule stabilizer, was examined in a model of acute edematous pancreatitis induced in rats by supramaximal stimulation with cholecystokinin analogue, caerulein. Prophylactic administration of taxol ameliorated inhibition of pancreatic digestive enzyme secretion, increased level of serum amylase, pancreatic edema, and histological alterations in this model. Immunofluorescence studies revealed that taxol stabilized the arrangement of microtubules by promoting tubulin polymerization. On the other hand, microtubule disorganization was found in rats without prophylactic taxol treatment. In caerulein-treated rats, there is microtubule disorganization which causes interference with intracellular vesicular transport leading to inhibition of pancreatic digestive enzyme secretion--a forerunner of acute pancreatitis. Taxol was found to prevent these events.
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PMID:The effect of microtubule stabilizer on rat caerulein-induced pancreatitis. 171 41

Effects of colchicine, a microtubule-disrupting agent, on rate exocrine pancreas were examined in comparison with the microtubule stabilizer Taxol for the purpose of analyzing the pathogenesis of cerulein-induced acute pancreatitis. Taxol ameliorated the inhibition of pancreatic secretion, elevation of serum amylase level, pancreatic edema, and histological alterations induced by supramaximal cerulein stimulation. In contrast, colchicine by itself and colchicine followed by cerulein stimulation (maximal and supramaximal) inhibited pancreatic secretion but did not induce the hyperamylasemia, pancreatic edema, or formation of large vacuoles, which characterized cerulein-induced pancreatitis. Electron microscopic studies in the colchicine-treated rats revealed that transport vesicles were accumulated in the supranuclear region and that no large vacuoles were observed in the apical lesion. Immunofluorescence studies confirmed that colchicine inhibited pancreatic secretion and disrupted the arrangement of microtubules. Posttreatment of colchicine did not prevent the development of cerulein-induced pancreatitis. Vinblastine, another microtubule-disrupting drug, as well as colchicine, inhibited pancreatic secretion but did not induce acute pancreatitis. The results obtained in this study suggest that microtubule disorganization at a specific step in the process of intracellular vesicular transport causes cerulein-induced pancreatitis and that this step is more apical than that at which colchicine inhibits secretion in the pancreatic acinar cell.
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PMID:Effect of the microtubule-disrupting drug colchicine on rat cerulein-induced pancreatitis in comparison with the microtubule stabilizer taxol. 857 85

The eukaryotic transcription factor nuclear factor-kappaB (NF-kappaB)/Rel is activated by a large variety of stimuli. It has been demonstrated that NF-kappaB/Rel is induced during the course of cerulein pancreatitis. Here, we show that NF-kappaB/Rel is differentially activated in pancreatic lobules. Cerulein induces NF-kappaB/Rel via activation of IkappaB kinase (IKK), which causes degradation of IkappaBalpha but not IkappaBbeta. Tumor necrosis factor-alpha-mediated IKK activation leads to IkappaBalpha and IkappaBbeta degradation. In contrast, oxidative stress induced by H(2)O(2) activates NF-kappaB/Rel independent of IKK activation and IkappaBalpha degradation; instead IkappaBalpha is phosphorylated on tyrosine. H(2)O(2) but not cerulein-mediated NF-kappaB/Rel activation can be blocked by stabilizing microtubules with Taxol. Inhibition of tubulin polymerization with nocodazole causes NF-kappaB/Rel activation in pancreatic lobules. These results propose three different pathways of NF-kappaB/Rel activation in pancreatic acinar cells. Furthermore, these data demonstrate that microtubules play a key role in IKK-independent NF-kappaB/Rel activation following oxidative stress.
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PMID:Different modes of NF-kappaB/Rel activation in pancreatic lobules. 1212 73