Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncostatin M (OM), a cytokine produced by macrophages and activated T cells, has been shown to be a potent inducer of liver low density lipoprotein receptor (LDLR) activity by increasing LDL uptake and cell surface LDLR number in HepG2 cells. To investigate whether OM regulates the transcription of the LDLR gene and if the effect is independent of the sterol pathway, we examined the effects of OM on the promoter activity of the LDLR gene and the expression of LDLR mRNA. HepG2 cells were transfected with hybrid genes containing three different lengths of DNA fragments from the 5' flanking region of the LDLR gene that were fused to the coding region of the chloramphenicol acetyltransferase (CAT) gene. OM induced an approximately 3-fold increase in CAT activities in pLDLR-CAT vector-transfected cells that were incubated in lipoprotein-depleted medium and a 6-fold increase in CAT activities when the transfected cells were treated with sterols. OM stimulated similar increases in CAT activities in HepG2 cells transfected with pLDLR-CAT 234, pLDLR-CAT 1563, and pLDLR-CAT 6500, suggesting that the essential cis-acting element that mediates the OM effect is located within the 177 base pairs upstream of the transcription start site of the LDLR gene. Examination of the regulation of the endogenous LDLR mRNA expression by OM gave results similar to those in transfected cells. OM increased the levels of mRNA of LDLR, regardless of the presence or absence of lipoprotein and sterols. These data suggest that the up-regulation of the LDLR by OM is at the transcriptional level through a nonsterol mediated mechanism.
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PMID:Oncostatin M activates low density lipoprotein receptor gene transcription in sterol-repressed liver cells. 769 81

Oncostatin M (OSM) regulates expression of various genes in connective tissue (CT) cells, including tissue inhibitor of metalloproteinases-1 (TIMP-1). In mouse fibroblast cell lines MLg, NIH 3T3 and primary mouse lung fibroblasts (MLF), murine OSM (muOSM) stimulated high TIMP-1 mRNA expression in comparison to leukemia inhibitory factor (LIF), epidermal growth factor (EGF), interleukin (IL)-1beta and transforming growth factor (TGF)beta. In cell signaling, muOSM induced strong phosphorylation of extracellular-signal regulated protein kinase (Erk) 1/2, p38 and Akt in addition to phosphorylation of signal transducer and activator of transcription (STAT) 1, STAT3 and STAT5 within 15 min. LIF and TGFbeta had no such effects. EGF stimulated comparable or lower Erk1/2, p38 and Akt phosphorylation while IL-1beta induced p38 phosphorylation in the fibroblast cell lines. The Erk1/2 inhibitor PD98059 and the p38 inhibitor SB203580 inhibited TIMP-1 mRNA response to muOSM, whereas the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 enhanced the TIMP-1 mRNA response in NIH 3T3 and MLg cells. PD98059 and SB203580, but not LY294002, also inhibited fold induction of a chloramphenicol acetyltransferase (CAT) reporter gene driven by a minimal TIMP-1 promoter that contained a proximal activator protein-1 (AP-1) site. Co-transfection with JunB or c-Jun expression vector in NIH 3T3 cells caused marked transactivation of the TIMP-1 promoter/CAT reporter gene. muOSM caused a rapid increase of JunB and c-Jun protein in NIH 3T3 cells. PD98059 partially inhibited the increase of JunB, but not c-Jun, whereas SB203580 did not induce detectable changes in expression of either AP-1 factor in response to muOSM. These results demonstrate that Erk1/2 and p38 contribute to the elevation of muOSM induced TIMP-1 expression, but PI3K does not, and suggest that Erk1/2 does so by enhancing JunB expression.
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PMID:Mitogen-activated protein kinases Erk1/2 and p38 are required for maximal regulation of TIMP-1 by oncostatin M in murine fibroblasts. 1524 7