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)

Cyclopentenone prostaglandins (PGs) are transported into cells and stimulate the expression of various stress genes, such as that coding for BiP (an ER luminal protein). To reveal the site of action of the PGs for the induction of stress-gene expression, we introduced a fluorescent probe, pyrene, into two types of PG analogue, GIF0010 (a cyclopentenone type) and GIF0037 (a cyclopentanone type) and examined their intracellular localization in normal rat kidney cells and their ability to induce the BiP gene expression. GIF0010 accumulated around the nuclei and coincided with BiP, a resident protein in the endoplasmic reticulum (ER) and markedly induced BiP gene expression. By contrast, GIF0037 and pyrene neither accumulated in the cell nor induced BiP gene expression. Thus the ER localization of GIF0010 and the induction of gene expression by GIF0010 are ascribed to the cyclopentenone structure. Treatment with cycloheximide inhibited both the accumulation of GIF0010 and the induction of the BiP mRNA, suggesting that the ER localization of the PG and subsequent gene expression require the nascent protein synthesis. These results demonstrate that the cyclopentenone PG is specifically accumulated in the ER, transducing a signal for BiP gene expression in the nuclei.
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PMID:Localization of a cyclopentenone prostaglandin to the endoplasmic reticulum and induction of BiP mRNA. 974 10

Environmental injury has been associated with endoplasmic reticulum (ER) stress, a response characterized by activation of the unfolded protein response, proteasomal degradation of proteins, and induction of HSPA5, also known as GRP78 or BiP. Although HSPA5 has been implicated in the stress response to environmental injury in several cell types, its role in the glomerular ER stress response is unknown. In this study, we evaluated HSPA5 activation profiles in rat glomerular mesangial cells (rGMCs) challenged with heavy metals (HgCl2 or Pb2+ acetate) or polycyclic aromatic hydrocarbons (PAHs, ie, benzo(a)pyrene [BaP]). Challenge of rGMCs with 1 or 10 microM HgCl2 or Pb2+ acetate increased HSPA5 mRNA and protein levels. The induction response was sensitive to transcriptional and translational inhibition by actinomycin D (AD) and cyclohexamide, respectively. HSPA5 mRNA was induced by 3 microM BaP in an AD-sensitive manner, but this response was unaffected by the presence of heavy metals. A promoter construct containing sequences that mediate thapsigargin (TH) inducibility of the HSPA5 promoter was refractory to both heavy metals and BaP. The HSPA5 induction response in rGMCs is conserved because it was reproduced with fidelity in immunolocalization experiments of HSPA5 protein in M15 and HEK293 cells in embryonic lines of murine and human origin, respectively. Collectively, these findings identify HSPA5 in the stress response of rGMCs and implicate regulatory mechanisms that are distinct from those involved in TH inducibility.
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PMID:Activation profiles of HSPA5 during the glomerular mesangial cell stress response to chemical injury. 1791 53

Engineered silica nanoparticles (SiO(2)-NPs) find widespread application and may lead to exposure of humans and the environment. Here we compare the effects of SiO(2)-NPs and SiO(2)-NPs doped with silver (SiO(2)-Ag-NPs) on survival and cellular function of human liver cells (Huh7) and Pimephales promelas (fathead minnow) fibroblast cells (FMH). In Huh7 cells we investigate effects on the endoplasmatic reticulum (ER), including ER stress, and interactions of nanoparticles (NPs) with metabolizing enzymes and efflux transporters. The NPs formed agglomerates/aggregates in cell culture media as revealed by SEM and TEM. SiO(2) and SiO(2)-1% Ag-NPs were taken up into cells as demonstrated by agglomerates occurring in vesicular-like structures or freely dispersed in the cytosol. Cytotoxicity was more pronounced in Huh7 than in FMH cells, and increased with silver content in silver-doped NPs. Dissolved silver was the most significant factor for cytotoxicity. At toxic and non-cytotoxic concentrations SiO(2)-NPs and SiO(2)-1% Ag-NPs induced perturbations in the function of ER. In Huh7 cells NPs induced the unfolded protein response (UPR), or ER stress response, as demonstrated in induced expression of BiP and splicing of XBP1 mRNA, two selective markers of ER stress. Additionally, SiO(2)-1% Ag-NPs and AgNO(3) induced reactive oxygen species. Pre-treatment of Huh7 cells with SiO(2)-1% Ag-NPs followed by exposure to the inducer benzo(a)pyrene caused a significant reduced induction of CYP1A activity. NPs did not alter the activity of ABC transporters. These data demonstrate for the first time that SiO(2)-NPs and SiO(2)-1% Ag-NPs result in perturbations of the ER leading to the ER stress response. This represents a novel and significant cellular signalling pathway contributing to the cytotoxicity of NPs.
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PMID:Silica nanoparticles and silver-doped silica nanoparticles induce endoplasmatic reticulum stress response and alter cytochrome P4501A activity. 2224 57