Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha 1-Antitrypsin (alpha 1 AT) is plasma glycoprotein that constitutes the principle inhibitor of neutrophil elastase in tissue fluids. It has been considered a prototype for liver-derived acute phase proteins in that its concentration in plasma increases three- to fourfold during the host response to inflammation/tissue injury. However, recent studies have shown that alpha 1 AT is expressed in several types of extrahepatic cells, including mononuclear phagocytes and enterocytes, and that there are distinct transcriptional units used in hepatocytes and at least one extra-hepatic cell type, blood monocytes. In this study, we have used a combination of ribonuclease protection assays, primer elongation analysis, and transcriptional run-on assays to further characterize mechanisms of basal and modulated alpha 1 AT gene expression in hepatocytes, enterocytes, and macrophages. The hepatoma cell line HepG2, intestinal epithelial cell line Caco2, and primary cultures of human peripheral blood monocytes were used as examples of the cell types. The results indicate that there are three macrophage-specific transcriptional initiation sites upstream from a single hepatocyte-specific transcriptional initiation site. Macrophages use these sites during basal and modulated expression. Hepatoma cells use the hepatocyte-specific transcriptional initiation site during basal and modulated expression but also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by the acute phase mediator interleukin 6 (IL-6). Caco2 cells use the hepatocyte-specific transcriptional initiation site during basal expression. There is a marked increase in the use of this site and an increase in the rate of transcriptional elongation of alpha 1 AT mRNA during differentiation of Caco2 cells from crypt-type to villous-type enterocytes. Caco2 cells also switch on transcription from the upstream macrophage transcriptional initiation sites during modulation by IL-6. These results provide further evidence that there are differences in the mechanisms of constitutive and regulated expression of the alpha 1 AT gene in at least three different cell types, HepG2-derived hepatocytes, Caco2-derived enterocytes and mononuclear phagocytes.
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PMID:Constitutive and modulated expression of the human alpha 1 antitrypsin gene. Different transcriptional initiation sites used in three different cell types. 155 83

Charge carried by the surface glycocalyx layer (SGL) of the cerebral endothelium has been shown to significantly modulate the permeability of the blood-brain barrier (BBB) to charged solutes in vivo. The cultured monolayer of bEnd3, an immortalized mouse cerebral endothelial cell line, is becoming a popular in vitro BBB model due to its easy growth and maintenance of many BBB characteristics over repeated passages. To test whether the SGL of bEnd3 monolayer carries similar charge as that in the intact BBB and quantify this charge, which can be characterized by the SGL thickness (L(f)) and charge density (C(mf)), we measured the solute permeability of bEnd3 monolayer to neutral solutes and to solutes with similar size but opposite charges: negatively charged alpha-lactalbumin (-11) and positively charged ribonuclease (+3). Combining the measured permeability data with a transport model across the cell monolayer, we predicted the L(f) and the C(mf) of bEnd3 monolayer, which is approximately 160 nm and approximately 25 mEq/L, respectively. We also investigated whether orosomucoid, a plasma glycoprotein modulating the charge of the intact BBB, alters the charge of bEnd3 monolayer. We found that 1 mg/mL orosomucoid would increase SGL charge density of bEnd3 monolayer to approximately 2-fold of its control value.
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PMID:Effect of surface charge of immortalized mouse cerebral endothelial cell monolayer on transport of charged solutes. 2008 68