Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clofibrate and many of its structural analogues induce proliferation of peroxisomes in the hepatic parenchymal cells of rodents and certain nonrodent species including primates. This induction is tissue specific, occurring mainly in the liver parenchymal cells and to a lesser extent in the kidney cortical epithelium. The induction of peroxisomes is associated with a predictable pleiotropic response, characterized by hepatomegaly, and increased activities and mRNA levels of certain peroxisomal enzymes. Using affinity chromatography, we had previously isolated a protein that binds to clofibric acid. We now show that this protein is homologous with the heat shock protein HSP70 family by analysis of amino acid sequences of isolated peptides from trypsin-treated clofibric acid binding protein and by cross-reactivity with a monoclonal antibody raised against the conserved region of the 70-kDa heat shock proteins. The clofibric acid-Sepharose column could bind HSP70 proteins isolated from various species, which could then be eluted with either clofibric acid or ATP. Conversely, when a rat liver cytosol containing multiple members of the HSP70 family was passed through an ATP-agarose column, and eluted with clofibric acid, only P72 (HSC70) was eluted. These results suggest that clofibric acid, a peroxisome proliferator, preferentially interacts with P72 at or near the ATP binding site.
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PMID:Identification of cytosolic peroxisome proliferator binding protein as a member of the heat shock protein HSP70 family. 237 Dec 72

Iprodione (C13H13Cl2N3O3) is a broad spectrum dicarboximide fungicide used on a wide variety of crop diseases. It is used on vegetables, ornamentals, pome and stone fruit, root crops, cotton and sunflowers, to control a variety of fungal pests. Iprodione inhibits the germination of spores and the growth of the fungal mycelium. Experimental studies with mice have indicated that exposure to iprodione at dose levels 5 to 15 folds greater than the LOAEL for liver injury, induces microsomal enzyme activities, hepatocyte proliferation, hepatomegaly, centrilobular hypertrophy, diffuse hypertrophy, and an increase in lauric acid hydroxylation. Currently, there is no toxicological data available on human health effects associated with exposure to iprodione. In this research, we performed the MTT Assay for cell viability to assess the cytotoxicity of iprodione, and the CAT-Tox (L) assay to measure the induction of stress genes in thirteen recombinant cell lines generated from human liver carcinoma cells (HepG2). The cytotoxicity data indicated a strong concentration-response relationship with regard to iprodione toxicity. The percentages of cell viability were 100 +/- 0%, 128.0 +/- 41.4%, 97.5 +/- 37.7%, 70.1 +/- 35.4%, 33.5 +/- 16.1%, and 5.1 +/- 3.7% in 0, 31.3, 62.5, 125, 250, and 500 microg/mL, respectively. The LC50 was 208.3 +/- 83.3 microg/mL. Data obtained from the CAT-Tox (L) assay showed that iprodione is able to induce a significant number of stress genes in HepG2 cells. At 250 ug/mL exposure, the induction levels were 1.2 +/- 0.4, 50.1 +/- 17.8, 3.9 +/- 1.2, 16.8 +/- 7.2, 10.7 +/- 0.7, 1.8 +/- 0, 26.3 +/- 10.0, 7.2 +/- 2.4, 1.8 +/- 0.0, 6.8 +/- 1.3, 6.7 +/- 0.5, and 4.3 +/- 1.8 for CYP1A1, GSTYa, XRE, HMTIIA, c-fos, NF-kBRE, HSP70, CRE, RARE, GADD153, GADD45, and GRP78, respectively. These results indicate that the metabolism of iprodione involves Phase II biotransformation in the liver (XRE, GSTYa), and that this chemical has the potential to cause cell proliferation and/or inflammatory reactions (c-fos, NF-kB), proteotoxic effects (HSP70, GRP78), metabolic disruption (CRE), and DNA damage (GADD45, GADD153).
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PMID:Cytotoxicity and transcriptional activation of stress genes in human liver carcinoma (HepG2) cells exposed to iprodione. 1669 76