Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Halothane causes an idiosyncratic hepatitis that is thought to result, in part, from immune reactions against one or more lumenal endoplasmic reticulum (ER) proteins that have been covalently modified by the trifluoroacetyl chloride metabolite of halothane. In this study, we have identified a 170 kDa protein target of halothane in the liver of rats. The 170 kDa protein was first detected when proteins in lysates of hepatocytes from halothane-treated rats were immunoprecipitated with antisera against several resident ER proteins. This 170 kDa protein was found to be associated with other protein targets of halothane, including protein disulfide isomerase, a protein disulfide isomerase isoform, a 59 kDa carboxylesterase, and 78 kDa glucose-regulated protein. Immunoblotting with antiserum directed against the trifluoroacetylated hapten indicated that the 170 kDa protein was trifluoroacetylated. Based upon its subcellular localization, molecular mass, N-terminal amino acid sequence, and antigenicity, the trifluoroacetylated 170 kDa protein was identified as UDP-glucose:glycoprotein glucosyltransferase (UGGT), a lumenal ER protein that is thought to have a role in the folding of N-linked glycoproteins. Moreover, treatment of rats with halothane caused a 44% decrease in the activity of liver microsomal UGGT, and at least 36% of the change in the activity of the enzyme could be due to a decrease in the level of the protein. The results suggest that the function of UGGT in folding of N-linked glycoproteins may be affected by other resident ER proteins or xenobiotics such as halothane.
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PMID:UDP-glucose:glycoprotein glucosyltransferase associates with endoplasmic reticulum chaperones and its activity is decreased in vivo by the inhalation anesthetic halothane. 907 3

Human hepatocellular carcinoma (HCC) is one of the commonest causes of mortality among solid organ malignancies. The incidence of HCC in the United States is rising. Few proteomic biomarker studies have been done in U.S. populations. Tumor and nonmalignant tissue from three American patients with hepatitis and non-hepatitis-associated HCC were analyzed to find common differences in protein expression. Proteins were separated by 2D electrophoresis (isoelectric focusing followed by 10% SDS-PAGE). Gels were fixed and then stained with Coomassie brilliant blue. Digitization and processing were performed using the PDQuest software. The Student's t-test was used to detect quantitative protein changes between tumor and nonmalignant liver consistent in all sample pairs with a cutoff made at P < 0.01. This yielded a total of 20 spots with significant (>2 fold) abundance changes. Matrix-assisted laser desorption ionization mass spectrometry analysis was performed using Waters Micomass M@LDI SYSTEM. The proteins were then identified using manual ProFound. Among the 20 spots, 10 showed overexpression and 10 showed underexpression in tumor. Overexpressed proteins included beta-5-tubulin, beta-actin, vimentin, hypermethylated in cancer 2 protein, heat-shock 70-kDa protein 9B, serum albumin, 39S ribosomal protein L45, butyrophilin, autoimmune regulator, and transcription factor ETV7. Underexpressed proteins included BiP protein, superoxide dismutase, peroxiredoxin 2, inoraganic pyrophosphatase, keratin 8, carbonic anhydrase 1, repulsive guidance molecule, catalase, C-1-tetrahydrofolate synthase, and hemoglobin alpha-2. Of particular interest, the protein autoimmune regulator was expressed 14-fold higher in tumor tissue, suggesting it may have a role in HCC. Validation and further investigation of these protein changes may lead to the discovery of new molecular targets for therapy, biomarkers for early detection, and new endpoints for therapeutic efficacy and toxicity.
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PMID:A pilot study of proteomic profiles of human hepatocellular carcinoma in the United States. 1953 95