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)

Insulin degradation enzyme (IDE) is a 110-kDa zinc metalloprotease found in the cytosol of all cells. IDE degrades insulin and a variety of small proteins including amyloid-beta. Recently, IDE has been proposed as the receptor for varicella-zoster virus (VZV) attachment. During our reassessment, some of the original studies were repeated and expanded in scope. We first confirmed that IDE antibody reduced VZV spread. For additional controls, we repeated the same experiments with herpes simplex virus (HSV)-infected cells as well as uninfected cells. There was a visible reduction in HSV spread but less than seen in the VZV system. Of greater importance, IDE antibody also inhibited the growth of uninfected cells. Second, we repeated the coprecipitation assays. We confirmed that antibodies to VZV gE (open reading frame 68) coprecipitated IDE and that anti-IDE antibody coprecipitated gE. However, the detected gE protein was not the mature 98-kDa form; rather, it was a precursor 73-kDa gE form found in the endoplasmic reticulum. Additional control experiments included VZV-infected cell cultures treated with tunicamycin to block gE glycosylation in the endoplasmic reticulum; again, the anti-IDE antibody coprecipitated a 73-kDa gE product. Finally, Orbitrap mass spectrometry analysis of a chromatographically purified gE sample revealed four cellular proteins associated with the unfolded protein response: BiP (HSPA5), HSPA8, HSPD1, and PPIA (peptidyl-propyl cis-trans isomerase). We conclude that IDE protease binds to the 73-kDa gE precursor and that this event occurs in the cytosol but not as a receptor/ligand interaction.
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PMID:Insulin-degrading enzyme binds to the nonglycosylated precursor of varicella-zoster virus gE protein found in the endoplasmic reticulum. 1986 91

Endoplasmic reticulum (ER) stress and oxidative stress appear to play a critical role in the progression of Parkinson's disease (PD). Insulin-like growth factor (IGF)-1, a 70-amino acid polypeptide trophic factor, acts as a potent neurotrophic, neurogenic, and neuroprotective/anti-apoptotic factor. In this study, we investigated the protective mechanisms of IGF-1 in rat pheochromocytoma PC12 cells exposed to the PD-related neurotoxin 6-hydroxydopamine (6-OHDA). The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates expression of genes required for free radical scavenging, detoxification of xenobiotics, and maintenance of redox potential. Exposure of cells to 6-OHDA resulted in an increase in ER-stress-induced apoptotic cell death, which was significantly reduced by treatment of cells with IGF-1. IGF-1 treatment significantly increased BiP and C/EBP homologous protein expression in 6-OHDA-treated cultures. IGF-1 protected cells from 6-OHDA-induced insult by inhibiting intracellular reactive oxygen species generation. Compared with vehicle-treated controls, the expression of Nrf2 and heme oxygenase-1 (HO-1) was increased in 6-OHDA-treated cells. IGF-1 significantly up-regulated HO-1 in cells exposed to 6-OHDA. These results suggest that IGF-1 augment cellular anti-oxidant defense mechanism, at least in part, through the up-regulation of HO-1 expression.
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PMID:Insulin-like growth factor-1 inhibits 6-hydroxydopamine-mediated endoplasmic reticulum stress-induced apoptosis via regulation of heme oxygenase-1 and Nrf2 expression in PC12 cells. 2270 70