Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell adhesion between circulating monocytes and the endothelium is a critical component of vascular thromboregulation and atherogenesis. The biochemical and genetic consequences of adhesion are poorly understood. We have found that monocyte surface expression of CD36, an integral membrane receptor for thrombospondin, collagen, and oxidized low density lipoprotein, increased dramatically upon adhesion to tumor necrosis factor-activated human umbilical vein endothelial cells (HUVEC). Expression was assessed by indirect immunofluorescence microscopy and immunoblotting using monoclonal antibodies to CD36. Steady-state CD36 mRNA levels, detected by RNase protection assay, also showed a similar pattern of up-regulation. To verify the adhesion dependence of the observed phenomenon, monocytes were co-cultured with tumor necrosis factor-activated HUVEC in a transwell apparatus that physically separated monocytes from the endothelial cells. Under these conditions, no increase in CD36 expression was detected, demonstrating that the enhanced monocyte CD36 expression observed is not due to soluble factors released by HUVEC. To characterize the specific adhesion molecules involved in the process, co-culture assays were performed on murine L cells transfected with either human E-selectin or intercellular adhesion molecule-1 cDNAs. A dramatic increase in CD36 mRNA was seen upon monocyte adhesion to E-selectin-transfected L cells compared with adhesion to intercellular adhesion molecule-1 or control transfectants. Furthermore, monoclonal antibodies to E-selectin inhibited the adhesion-dependent up-regulation of CD36 mRNA induced by transfected L cells or cytokine-activated endothelial cells. These findings demonstrate adhesion-dependent gene regulation of monocyte CD36 and suggest the possible involvement of E-selectin in initiating this process.
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PMID:CD36 induction on human monocytes upon adhesion to tumor necrosis factor-activated endothelial cells. 753 9

CD36 is an 88-kD integral membrane protein expressed on platelets, monocytes, macrophages, certain microvascular endothelia, and retinal pigment epithelium. It functions as an adhesive receptor for thrombospondin-1 (TSP-1), collagen, and malaria-infected erythrocytes and as a scavenger receptor for oxidized LDL and photoreceptor outer segments. The CD36-TSP-1 interaction plays a role in cell adhesion and the phagocytosis of apoptotic cells by macrophages. Because of the potential importance of the CD36-TSP-1 interaction in mediating atherogenic and inflammatory processes, we studied their expression in human peripheral blood monocytes exposed to soluble mediators known to regulate inflammation and atherogenesis. RNase protection assays showed 6- to 12-fold increases in CD36 mRNA in response to interleukin-4, monocyte colony-stimulating factor, and phorbol myristate acetate, while lipopolysaccharide and dexamethasone strongly downregulated CD36 mRNA. The downregulation of CD36 mRNA was associated with the disappearance of surface expression of CD36 antigen and loss of TSP-1 surface-binding capacity. Upregulation of CD36 mRNA was associated with a modest increase in surface antigen expression and a larger expansion of an intracellular pool of CD36. As with CD36, monocytes treated with monocyte colony-stimulating factor showed a rapid increase in TSP-1 mRNA expression. Moreover, while dexamethasone treatment decreased CD36 expression, it resulted in a rapid increase in TSP-1 mRNA, and while PMA increased CD36 mRNA, it rapidly decreased TSP-1 expression. Interferon gamma, which had no effect on CD36 mRNA, rapidly increased steady-state TSP-1 mRNA. Thus, expression of both CD36 and its ligand TSP-1 is regulated by soluble mediators, although certain mediators induce concordant changes and others discordant changes.
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PMID:Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators. 869 41

CD36 is a multifunctional integral-membrane glycoprotein that acts as a receptor for thrombospondin, collagen, long-chain fatty acids, and oxidized LDL. Platelet CD36 deficiency can be divided into two groups. In type I, neither platelets nor monocytes/macrophages express CD36; in type II, monocytes/macrophages express CD36 but platelets do not. Two known mutations cause CD36 deficiency, ie, a 478C-->T substitution in codon 90 (proline90-->serine) and a dinucleotide deletion at nucleotide 539 in codon 110. In this study we investigated a type I Japanese subject (A.T.) and identified a new mutation, a single nucleotide insertion at nucleotide 1159 in codon 317. This mutation leads to a frameshift and the appearance of a premature stop codon. CD36 gene analysis indicated that A.T. was a compound heterozygote for a dinucleotide deletion at nucleotide 539 and the single nucleotide insertion at nucleotide 1159. RNase protection studies suggested that the new mutation as well as the dinucleotide deletion led to a marked reduction in the level of CD36 mRNA in her macrophages. However, the new mutation could be detected in macrophage but not platelet CD36 mRNA. These data suggest that the allele having the single nucleotide insertion in this subject has an additional abnormality that results in the absence of the mutated CD36 mRNA in platelets.
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PMID:A single nucleotide insertion in codon 317 of the CD36 gene leads to CD36 deficiency. 869 42

CD36 is a glycoprotein with an Mr of 88 kDa that is expressed on platelets, monocytes/macrophages, capillary endothelial cells, and adipocytes. We previously demonstrated that CD36 is involved in the uptake of oxidized low density lipoprotein (OxLDL) by using CD36-deficient macrophages (J Clin Invest. 1995;96:1859). However, the regulation of CD36 expression in human monocyte-derived macrophages has not been fully elucidated. The current study attempted to clarify the effect of OxLDL and cytokines, both of which are present in atherosclerotic lesions and may play an important role in atherogenesis, on the expression of CD36. A cell enzyme-linked immunosorbent assay and flow cytometry were used to detect CD36 protein. A ribonuclease protection assay was used to measure CD36 mRNA in human monocyte-derived macrophages. The expression of CD36 was increased during the differentiation of monocytes to macrophages. Incubation of macrophages with 25 microg/mL OxLDL for 24 hours increased the level of CD36 protein by 56% and that of CD36 mRNA by 58%. Lysophosphatidylcholine did not affect the expression of CD36. The effects of OxLDL were demonstrated in macrophages that had already differentiated to the point where CD36 expression was almost maximal. Interferon-gamma (IFN-gamma) reduced the expression of CD36 in a dose-dependent manner. A concentration of 1000 U/mL IFN-gamma significantly reduced the expression of CD36 protein by 57% and that of CD36 mRNA by 30%. In conclusion, CD36 may be important in the formation of foam cells by induction through its ligand (OxLDL). Moreover, some local factors, such as IFN-gamma, may suppress CD36 expression on macrophages in human atherosclerotic lesions.
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PMID:Oxidized LDL increases and interferon-gamma decreases expression of CD36 in human monocyte-derived macrophages. 971 44

-CD36 is 1 of the class B scavenger receptor expressed on monocytes, monocyte-derived macrophages (Mphi), platelets, and adipocytes. In our previous studies, we reported that the uptake of oxidized low density lipoproteins (OxLDLs) is reduced by approximately 50% in Mphi from CD36-deficient patients compared with that in control subjects. Recently, we have shown that CD36 is highly expressed in human atherosclerotic aorta. Possibilities have been raised that besides the wide distribution and multifunctional characteristics of CD36, this molecule may also be involved in the mediation of intracellular signaling. The aim of the present study was to elucidate the role of CD36 in cytokine secretion and to investigate the CD36-mediated intracellular signaling stimulated by OxLDL. On addition of OxLDL or thrombospondin-1, the Mphi from CD36-deficient patients secreted significantly less amounts of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) compared with those from controls. RNase protection assay with multiprobe template sets demonstrated that after incubation with OxLDL, the mRNAs of a variety of cytokines, including genes encoding IL-1Ra, IL-1beta, IL-6, TNF-alpha and -beta, and interferon (IFN)-gamma and -beta, were significantly lower in the Mphi of patients. The addition of antibody against CD36 attenuated this OxLDL-induced response in controls. We also observed a reduced response in nuclear factor-kappa B (NF-kappa B) activity in OxLDL-stimulated Mphi from CD36-deficient patients. Unlike OxLDL, stimulation by lipopolysaccharide induced an increase in NF-kappa B activity in Mphi from CD36-deficient patients, suggesting that lipopolysaccharide-mediated signaling was conserved. These results demonstrate that in addition to the reduced OxLDL uptake that we reported previously, CD36-deficient patients may also have an impaired response of OxLDL-induced NF-kappa B activation and subsequent cytokine expression.
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PMID:Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients. 1093 17

The present study examined the roles of peroxisome proliferator-activated receptors (PPAR) in activation of hepatic stellate cells (HSC), a pivotal event in liver fibrogenesis. RNase protection assay detected mRNA for PPARgamma1 but not that for the adipocyte-specific gamma2 isoform in HSC isolated from sham-operated rats, whereas the transcripts for neither isoforms were detectable in HSC from cholestatic liver fibrosis induced by bile duct ligation (BDL). Semi-quantitative reverse transcriptase-polymerase chain reaction confirmed a 70% reduction in PPARgamma mRNA level in HSC from BDL. Nuclear extracts from BDL cells showed an expected diminution of binding to PPAR-responsive element, whereas NF-kappaB and AP-1 binding were increased. Treatment of cultured-activated HSC with ligands for PPARgamma (10 microm 15-deoxy-Delta(12,14)-PGJ(2) (15dPGJ(2)); 0.1 approximately 10 microm BRL49653) inhibited DNA and collagen synthesis without affecting the cell viability. Suppression of HSC collagen by 15dPGJ(2) was abrogated 70% by the concomitant treatment with a PPARgamma antagonist (GW9662). HSC DNA and collagen synthesis were inhibited by WY14643 at the concentrations known to activate both PPARalpha and gamma (>100 microm) but not at those that only activate PPARalpha (<10 microm) or by a synthetic PPARalpha-selective agonist (GW9578). 15dPGJ(2) reduced alpha1(I) procollagen, smooth muscle alpha-actin, and monocyte chemotactic protein-1 mRNA levels while inducing matrix metalloproteinase-3 and CD36. 15dPGJ(2) and BRL49653 inhibited alpha1(I) procollagen promoter activity. Tumor necrosis factor alpha (10 ng/ml) reduced PPARgamma mRNA, and this effect was prevented by the treatment with 15dPGJ(2). These results demonstrate that HSC activation is associated with the reductions in PPARgamma expression and PPAR-responsive element binding in vivo and is reversed by the treatment with PPARgamma ligands in vitro. These findings implicate diminished PPARgamma signaling in molecular mechanisms underlying activation of HSC in liver fibrogenesis and the potential therapeutic value of PPARgamma ligands for liver fibrosis.
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PMID:Peroxisome proliferator-activated receptors and hepatic stellate cell activation. 1096 82

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