Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human lung fibroblasts differing in C1q binding, steady-state levels of collagen synthesis, and other functional properties were isolated. Explants of normal human lung specimens were cultured in medium containing complement-inactivated plasma-derived human serum or complete human serum. Cells obtained were treated with C1q and fluorescein isothiocyanate-anti-C1q antibody and separated based on fluorescence intensity in a fluorescence-activated cell sorter (FACS). FACS profiles showed that fibroblasts obtained in the presence of plasma-derived serum (HF cells) displayed higher fluorescence intensity than those obtained in complete serum (LF cells). The unsorted and sorted HF and LF fibroblasts retained their respective fluorescence phenotypes after subculture. The LF fibroblasts proliferated faster than HF cells and contained more cycling cells. However, whereas the sorted HF cells grew normally, sorted LF cells grew poorly. Collagen production and pro alpha l[I] mRNA levels in HF cells were 2.6 +/- 0.7 and 2.1 +/- 0.6 times as high as LF cells (n = 4). Collagen synthesis in both HF and LF cells was stimulated by transforming growth factor-beta and inhibited by interferon-gamma, but the stimulation was greater and inhibition less in LF cells. Our results indicate that C1q binding and the type of C1q receptors can serve as markers for fibroblast subpopulations differing in collagen synthesis, and that selection of subpopulations and their differential sensitivity to regulatory molecules can contribute to collagen alterations associated with inflammation, fibrosis, and other acquired diseases.
Am J Respir Cell Mol Biol 1992 Apr
PMID:Human lung fibroblast subpopulations with different C1q binding and functional properties. 155 Jun 83

The Arg-Gly-Asp peptide (RGD), contained in several extracellular matrix proteins such as fibronectin, laminin, vitronectin, and collagen, is a tripeptide that plays a role as a recognition sequence in many cell-to-cell and cell-to-matrix adhesion mechanisms, through its interaction with several receptors of the integrin family. We previously described the ability of the oolemma of hamster oocytes to bind GRGDTP coupled to the surface of activated immunobeads and demonstrated that RGD-containing oligopeptides inhibit the adhesion of human and hamster spermatozoa to zona-free hamster oocytes and their subsequent penetration. In the present experiments, we show, utilizing immunobeads coated with an RGD-containing peptide (PepTiteTM 2000), that the oolemma of unfertilized human eggs is also able to recognize this adhesion sequence. The binding of PepTiteTM 2000-coated immunobeads to the oolemma was inhibited by the oligopeptide GRGDTP as well as by fibronectin and laminin. When immunobeads were prepared with a PepTiteTM concentration of 10 micrograms/ml, GRGDTP 150 micrograms/ml, laminin 80 micrograms/ml, and fibronectin 60 micrograms/ml inhibited bead rosetting on the egg surface. These data suggest that a specific binding moiety for RGD is present on the human egg surface. The binding of fibronectin to the oolemma was also demonstrated by the rosetting of immunobeads coupled with antifibronectin antibody to human oocytes after their exposure to 1 mg/ml free fibronectin. Such binding of fibronectin to the oolemma could be inhibited by coincubation with a monoclonal antibody directed against the cell adhesion fragment of fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Reprod Dev 1992 Mar
PMID:Evidence for the presence of an integrin cell adhesion receptor on the oolemma of unfertilized human oocytes. 155 7

We recently described a new type of assembly of collagen molecules, forming typical liquid crystalline phases in highly concentrated solutions after sonication. The present work shows that intact 300 nm long collagen molecules also form cholesteric liquid crystalline domains, but the time required is much longer, several weeks instead of several days. Differential calorimetry and X-ray diffraction show that sonication does not alter the triple-helical structure of the collagen fragments. In the viscous solutions, observed between crossed polars in optical microscopy, the textures vary as a function of the concentration. Molecules first align near the air interface at the coverslip edge, then as the concentration increases by slow evaporation of the solvent, the birefringence extends inwards and liquid crystalline domains progressively appear. For concentrations estimated to be above 100 mg/ml, typical textures and defects of cholesteric phases are obtained, at lower concentrations zig-zag extinction patterns and banded patterns are observed; all these textures are described and interpreted. The cholesteric packing of collagen fibrils in various extracellular matrices is known, and the relationship that can be made between the ordered phases obtained with collagen molecules in vitro and the related geometrical structures observed between fibrils in vivo is thoroughly discussed.
J Mol Biol 1992 Apr 05
PMID:Liquid crystallinity in condensed type I collagen solutions. A clue to the packing of collagen in extracellular matrices. 156 62

We have studied collagen synthesis and secretion in an established liver connective tissue cell line (GRX) that can be induced in vitro to express either the myofibroblastic or the fat-storing (lipocyte) phenotype. In lipocytes, collagen synthesis was reduced. Their intracellular collagen degradation corresponded to 15% of newly synthesized collagen. In myofibroblasts, collagen synthesis was high but its secretion was considerably altered by intracellular collagen degradation, which attained up to 60% of newly synthesized collagen. In this in vitro model, we have provided direct evidence that hepatic lipocytes, involved mainly in lipid and retinol metabolism, have a low basal level of collagen synthesis. Myofibroblastic phenotype correlates with increased collagen synthesis and may be directly related to increased collagen deposition in hepatic fibrosis. Modulation of the phenotype of liver connective tissue cells are possibly one of the major points of control in normal and pathological deposition of collagen in liver parenchyma.
Exp Mol Pathol 1992 Apr
PMID:Collagen synthesis in an established liver connective tissue cell line (GRX) during induction of the fat-storing phenotype. 158 37

Cultured glomerular mesangial cells (MCs) have the ability to contract the surrounding collagen gel matrix (CGM). To investigate this phenomenon, we examined the effect of growth factors and extracellular matrix (ECM) components. Among some growth factors tested, transforming growth factor-beta (TGF-beta) and fetal calf serum (FCS) enhanced CGM contraction dose dependently. These factors acted through distinct mechanisms because: (1) when growth-arrested MCs were used, the effect of FCS was inhibited partially but that of TGF-beta was not; and (2) anti-TGF-beta had no influence on CGM contraction induced by FCS. Among the ECM components such as laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin), which were each mixed separately with CGM before gelling, heparin-like proteoglycans and type IV collagen inhibited contraction by MCs. The inhibitory effect of heparin was mediated by the interaction both with CGM and with MCs because: (1) when heparin was added to the culture medium, not into the gel, the inhibitory effect was diminished but still noted; and (2) using growth-arrested MCs, the inhibitory effect of heparin in the medium was reduced but still observed. This culture assay is useful for elucidating the tensional interaction between MCs and surrounding ECM.
Exp Mol Pathol 1992 Apr
PMID:Extracellular matrix contraction by cultured mesangial cells: modulation by transforming growth factor-beta and matrix components. 158 39

The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema linked to a deficiency of serum antielastase. In this mouse occurrence of connective tissue abnormalities in various organs (systemic scleroderma) has been reported. The aim of the present work was to study lung collagen synthesis and deposition in Tsk mice. No differences in the collagen synthesis rate and morphology at the ultrastructural level were found in Tsk mice at birth. At 2 months of age, a marked increase in collagen was observed within the alveolar septa. At this time, an increased lung collagen synthesis, assessed by determining prolyl hydroxylase activity and incorporation of radiolabeled proline, was found in Tsk mice with respect to control mice. However, due to the ongoing parenchymal destruction, the values of total lung collagen at 6 and 12 months of age were only moderately but significantly increased with respect to those observed at 2 months. As a consequence, a progressive accumulation of lung collagen fibers was observed in the residual septa. The increase in collagen deposition was accompanied by a relative increase in type I collagen. Although the data in the literature would suggest a genetic cause for the lung collagen change in Tsk mice, the data presented here indicate that the change in lung collagen metabolism may be a part of a remodeling process taking place after lung destruction.
Exp Mol Pathol 1992 Apr
PMID:Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema. 158 42

As an approach to understanding physiological mechanisms that control the proliferation of highly differentiated cells, we are addressing whether certain hepatic transcription factors participate in mechanisms that control the growth of hepatocytes. We have focused on CCAAT enhancer-binding protein (C/EBP alpha), a transcription factor which is highly abundant in normal liver and is considered to regulate expression of many genes, including some involved in energy metabolism (S. L. McKnight, M. D. Lane, and S. Gluecksohn-Walsh. Genes Dev. 3:2021-2024, 1989). Using Northern (RNA) blot analysis, we have examined the expression of C/EBP alpha mRNA during liver regeneration and in primary cultures of hepatocytes. C/EBP alpha mRNA levels decrease 60 to 80% within 1 to 3 h after partial hepatectomy as the cells move from G0 to G1 and decrease further when cells progress into S phase. Run-on transcription analysis is in agreement with the Northern blot data, thus suggesting that C/EBP alpha is transcriptionally regulated in regenerating liver. C/EBP alpha mRNA expression also decreases dramatically during the growth of freshly isolated normal hepatocytes cultured under conventional conditions (on dried rat tail collagen; stimulated to proliferate by epidermal growth factor [EGF] and insulin). Cultures of hepatocytes on rat tail collagen in the presence or absence of EGF clearly show that within 3 h, EGF depresses C/EBP alpha mRNA expression and that this effect is substantially greater by 4 h. Inhibition of protein synthesis in the liver by cycloheximide or in cultured hepatocytes by puromycin or cycloheximide effectively blocks the down-regulation of C/EBP alpha gene expression, apparently by stabilizing the normal rapid turnover of the C/EBP alpha mRNA (half-life of <2 h). This drop in C/EBP alpha gene expression in response to activation of hepatocyte growth is consistent with the proposal that C/EBP alpha has an antiproliferative role to play in highly differentiated cells (R. M. Umek, A. D. Friedman, and S. L. McKnight, Science 251: 288-292, 1991).
Mol Cell Biol 1992 Jun
PMID:Growth-dependent inhibition of CCAAT enhancer-binding protein (C/EBP alpha) gene expression during hepatocyte proliferation in the regenerating liver and in culture. 158 57

Prednisone, prednisolone, and methylprednisolone are currently administered in association with cyclosporin A in the postoperative treatment of transplant patients. The aim of this work was to evaluate the effects of these corticosteroids on the expression of several forms of cytochromes P450 (P450), including P450 1A2, 2D6, 2E1, and 3A, and on cyclosporin A oxidase activity in human liver. For this purpose, human hepatocytes prepared from lobectomies were maintained in culture in a serum-free medium, in collagen-coated dishes, for 96-144 hr, in the absence or presence of 50-100 microM corticosteroids, rifampicin, or dexamethasone. To mimic more closely the current clinical protocol, hepatocyte cultures were also co-treated with corticosteroids and cyclosporin A or ketoconazole (a selective inhibitor of P450 3A). Cyclosporin A oxidase activity, intracellular retention of cyclosporin A oxidized metabolites within hepatocytes, accumulation of P450 proteins and corresponding messages, and de novo synthesis and half-lives of these P450 were measured in parallel in these cultures. Our results, obtained from seven different hepatocyte cultures, showed that 1) dexamethasone and prednisone, but not prednisolone or methylprednisolone, were inducers of P450 3A, at the level of protein and mRNA accumulation, as well as of cyclosporin A oxidase activity, known to be predominantly catalyzed by these P450; 2) although corticosteroids are known to be metabolized in human liver, notably by P450 3A, partial or total inhibition of this P450 by cyclosporin or ketoconazole, respectively, did not affect the inducing efficiency of these molecules; 3) corticosteroids did not affect the half-life of P450 3A or the accumulation of other forms of P450, including 1A2, 2D6, and 2E1; 4) chronic treatment of cells with cyclosporin did not affect P450 3A accumulation; 5) corticosteroids were all competitive inhibitors of cyclosporin A oxidase in human liver microsomes, with Ki values of 61 +/- 12, 125 +/- 25, 190 +/- 38, and 210 +/- 42 microM for dexamethasone, prednisolone, prednisone, and methylprednisolone, respectively; and 6) chronic treatment of cells with corticosteroids did not influence the excretion of oxidized metabolites of cyclosporin from the cells. These results support most of clinical reports dealing with mutual interactions between cyclosporin A and corticosteroids.
Mol Pharmacol 1992 Jun
PMID:Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. 161 9

An investigation of myocardial glycoproteins was undertaken to elucidate the molecules responsible for the periodic acid-Schiff (PAS) reactivity of the increased extracellular matrix of diabetic cardiomyopathy. Perfusion with radiolabeled mannose indicated an enhanced formation of matrix components in the diabetic compared to the normal rat heart. Electrophoretic separation of radiolabeled extracts demonstrated the presence of glycoproteins with Mr values of 205, 142 and 90 kDa which could be separated by Bio-Gel A-5 m filtration. Fractionation of non-perfused hearts resulted in the isolation of only the 205 and 142 kDa components, which were shown by amino acid analyses and collagenase digestion to belong to the collagen family of proteins and by immunoblotting to represent type VI collagen. The carbohydrate content of these rat myocardial type VI collagen subunits, determined from monosaccharide analyses, was 11 and 12%, respectively, and N-glycanase digestion of the 142 kDa chain resulted in a decrease in size of approximately 14 kDa, indicating the presence of asparagine-linked units. Examination of normal and diabetic rat heart sections indicated that the latter contained abundant PAS-positive strands and nodules which corresponded to the distribution of anti type VI collagen reactivity. Moreover, immunoblots showed higher levels of Type VI collagen in diabetic than in normal heart extracts. Type VI collagen therefore appears to represent a major glycoprotein of myocardial extracellular matrix and to be implicated in diabetic cardiomyopathy.
J Mol Cell Cardiol 1992 Apr
PMID:Myocardial glycoproteins in diabetes: type VI collagen is a major PAS-reactive extracellular matrix protein. 161 69

Using live, intact Ascaris suum and a closed perfusion system, the absorption kinetics and tissue distribution of selected radiolabeled permeants were measured to determine the importance of the transcuticular pathway for drug absorption. The data support the conclusions established by previous in vitro transport studies which utilized excised cuticle-hypocuticle tissue preparations. The external surface of A. suum can be breached by drugs and the rate-determining barrier is the lipoidal hypocuticle tissue, provided the permeant is sufficiently small to traverse the aqueous-filled, negatively charged collagen matrix of the cuticle. The ex vivo permeability coefficients of the model permeants for the cuticle-hypocuticle barrier were in good quantitative agreement with the in vitro permeability coefficients. The lipophilic permeants hydrocortisone and p-nitrophenol were preferentially distributed in the gut tissue, whereas the hydrophilic permeant urea was distributed evenly throughout the organism and was extensively metabolized. Ligated and nonligated A. suum showed no significant differences in either uptake kinetics or tissue distribution of the permeants. This indicates that the transcuticular pathway is the major route of drug absorption as compared to oral ingestion.
Mol Biochem Parasitol 1992 May
PMID:Mechanistic studies in the transcuticular delivery of antiparasitic drugs. II: Ex vivo/in vitro correlation of solute transport by Ascaris suum. 162 97


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