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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Filters comprising multiple layers of rabbit renal tubular basement membrane were constructed with conventional pressure filtration chambers. The effects of concentration-polarization on the behaviour of these filters was assessed by studying the filtration of proteins and of serum under turbulent (stirred) and unstirred conditions. 2. With stirring bovine serum albumin was effectively rejected by the filter barriers (sigma = 0.95) but rejection was diminished (sigma = 0.18) without stirring. The hydraulic permeability of the filters also fell without stirring. 3. In the presence of horse immunoglobulin G, a wholly rejected protein, the rejection of cytochrome c was increased and hydraulic flux was reduced. 4. Filtration studies of serum showed that serum protein was effectively rejected with stirring (sigma greater than 0.999) but rejection diminished when stirring ceased (sigma = 0.98). Albumin was the only protein detected in the filtrate with stirring but alpha- and beta- globulins appeared when stirring ceased. 5. These results show that concentration-polarization markedly affects the behaviour of these basement membrane filters in vitro, since without stirring a polarization layer of rejected protein is formed, which reduces hydraulic permeability and results in increased protein permeation through the filter.
Clin Sci Mol Med 1978 Jul
PMID:Effects of concentration-polarization on the filtration of proteins through filters constructed from isolated renal basement membrane. 66 63

Phenotypes of the cells developing into small colonies after days of primary culture of adult rat hepatocytes in serum-free modified Dulbecco Modified Eagles' medium containing 10 mM nicotinamide and 10 ng/ml epidermal growth factor were analyzed immunocytochemically, cytochemically and ultrastructurally. Albumin, cytokeratin 8 and 18 were seen by immunocytochemical techniques in the cells of the small colonies at Day 6. Transferrin, alpha 1-antitrypsin, ceruloplasmin, and haptoglobin, proteins secreted by mature hepatocytes, were faintly stained in these cells as was alpha-fetoprotein. These proteins were secreted into the culture medium as evidenced by immunoblot analysis. gamma-Glutamyltransferase, alkaline phosphatase and glucose 6-phosphatase were not present in the cells of the small colonies as well as the surrounding hepatocytes at Day 6 of culture. In addition, ultrastructural examinations of the cells in the small colonies indicated that these cells not only had many characteristic mitochondria and desmosomes, but also a few small peroxisomes. Such cells, even after 20 days in culture were proliferating, as evidenced by the intranuclear presence of the proliferating cell nuclear antigen. The potential relation of these cells to hepatocytes which may serve as the principal reserve for replicating hepatocytes is discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Characteristics of small cell colonies developing in primary cultures of adult rat hepatocytes. 127 92

Estradiol 17 beta-hydroxysteroid dehydrogenase (E2DH) is the enzyme responsible for the interconversion of estrone (E1), and the more biologically potent steroid, estradiol (E2), and has a crucial role in regulating breast tissue concentrations of E2. It has previously been shown that breast tumor cytosol is able to preferentially stimulate the reductive conversion of E1 to E2 in cultured MCF-7 breast cancer cells. In this study the stimulatory factor(s) from breast tumor cytosol have been partially purified by gel filtration and affinity chromatography. Human serum albumin (HSA) has been identified as a component of this bioactive fraction. Subsequent testing of commercially purified HSA preparations has revealed the ability of some preparations to be highly stimulatory. The albumin present in breast tumor cytosol may therefore be a contributing factor to the observed stimulation of reductive E2DH activity in cultured MCF-7 cells. Such a mechanism may account in part for the higher concentrations of E2 which are observed in breast tumors in vivo.
Mol Cell Endocrinol 1992 Jan
PMID:Identification of albumin in breast tumor cytosol as a factor involved in the stimulation of estradiol 17 beta-hydroxysteroid dehydrogenase (reductive) activity. 155 73

Pentoxifylline, a methylxanthine with phosphodiesterase inhibitor activity, attenuates endotoxin-induced pulmonary vascular protein leak and decreases lung neutrophil accumulation in vivo. In vitro, pentoxifylline decreases neutrophil activation as measured by superoxide release and phagocytosis of latex beads. To test the hypothesis that the beneficial effect of pentoxifylline may be via a direct effect on the endothelial cells as well as via prevention of neutrophil activation, we incubated bovine pulmonary artery endothelial cell monolayers with endotoxin and pentoxifylline in the presence or absence of human neutrophils. Albumin clearance across the monolayers was used as an index of endothelial permeability. Endotoxin (1.0 micrograms/ml) increased albumin clearance in a dose- and time-dependent fashion (207.5 +/- 25%, P less than 0.05). Co-incubation with neutrophils enhanced this effect. Pentoxifylline significantly attenuated the endotoxin-induced increase in albumin clearance both with and without neutrophils, and lessened endotoxin-induced cell lysis (chromium release) and morphologic changes. Because increased endothelial cyclic adenosine monophosphate (cAMP) levels may decrease protein permeability and pentoxifylline increases cAMP in neutrophils, we measured cAMP levels in endothelial cells. Incubation with pentoxifylline failed to raise cAMP levels in endothelial cells, in contrast to incubation with aminophylline. In conclusion, pentoxifylline attenuates endotoxin-induced increase in albumin clearance across endothelial monolayers both in the presence and absence of neutrophils. These results suggest that part of the protective effect of pentoxifylline may be mediated via effects on endothelium. Furthermore, this pentoxifylline-mediated endothelial barrier effect appears to be independent of an effect on cAMP.
Am J Respir Cell Mol Biol 1991 Mar
PMID:Pentoxifylline lessens the endotoxin-induced increase in albumin clearance across pulmonary artery endothelial monolayers with and without neutrophils. 184 85

We present a strategy to elucidate the rate-limiting steps in activation of carcinogenic compounds by cytochromes P450. The principle was to select Reuber rat hepatoma cells for resistance to a procarcinogen. The hypothesis was that resistant cells should be systematically deficient in the P450 enzyme(s) involved in the activation process. Here we present an example of the use of this approach using aflatoxin B1 (AFB1), a potent hepatocarcinogen, as the selective agent. Parental cells as well as individual and pooled colonies selected for AFB1 resistance from three independent rat hepatoma lines were characterized for their content of 1) mRNA hybridizing to cDNA and/or oligonucleotide probes for cytochromes P450IIB1, P450IIB2 and albumin; and 2) aldrin epoxidase activity. Parental aflatoxin B1-sensitive cells were shown to express P450IIB1 but not P450IIB2. The majority of the aflatoxin B1-resistant clones failed to accumulate cytochrome P450IIB1 mRNA and expressed no or only very low aldrin epoxidase activity. Albumin mRNA levels remained unchanged, demonstrating that loss of expression of cytochrome P450IIB1 was not a consequence of a general dedifferentiation event. A revertant population showing restoration of both cytochrome P450IIB1 mRNA accumulation and aldrin epoxidase activity was fully sensitive to aflatoxin B1. The correlation between expression of cytochrome P450IIB1 and sensitivity to aflatoxin B1 in both parental cells and revertants strongly suggests that cytochrome P450IIB1 is a major contributor to the activation of aflatoxin B1 in rat hepatoma cells. The kind of strategy described here could be applied to other compounds that become cytotoxic for hepatoma cells following activation by cytochromes P450.
Mol Gen Genet 1990 Jul
PMID:Genetic analysis of aflatoxin B1 activation in rat hepatoma cells. 212 92

The effect of interleukin (IL)-6 and IL-1 on the biosynthesis of complement components C3, factor B, C2, C4 and C1 inhibitor (C1 inh), as well as that of albumin, was studied in vitro in human hepatoma-derived cell line, HepG2. Measuring the amounts of secreted complement proteins we detected a significant upregulation of C3 by both hormones. The enhancement of the factor B and especially that of C1 inh production was predominant by IL-6. In our experimental system neither IL-1 nor IL-6 affected the biosynthesis of C2 and C4. Albumin secretion was significantly decreased only in the simultaneous presence of IL-1 and IL-6. Detection of the changes in the amounts of C3- and factor B-specific mRNA of HepG2 cells suggests a pretranslational regulation by these cytokines. The secretion of C3 and factor B was markedly potentiated when IL-1 and IL-6 were added together. However only the gene expression of factor B, but not of C3, was found to reveal synergism. IL-6 enhanced the in vitro production of C3 in mouse hepatocytes as well. This effect was greatly potentiated in the presence of histamine.
Mol Immunol 1990 Feb
PMID:Hormonal regulation of complement biosynthesis in human cell lines--II. Upregulation of the biosynthesis of complement components C3, factor B and C1 inhibitor by interleukin-6 and interleukin-1 in human hepatoma cell line. 215 45

Both estrogens and androgens have been shown to stimulate sex hormone binding globulin (SHBG) secretion in vitro in the hepatocellular carcinoma cell line, Hep G2, in contrast to the expected inhibition by androgens from in vivo studies. However, such in vitro stimulation was only demonstrated at high steroid doses, generally in serum-containing medium, with added Phenol Red. In the present study, Hep G2 cells were grown in serum-free medium, without Phenol Red, under the influence of testosterone (T) (0, 0.5-500 nM) and ethinyl estradiol (EE2) (0, 50 pM-500 nM). Levels of secreted SHBG and albumin were correlated with androgen receptors in cytosolic (ARc) and nuclear (ARn) fractions and with DNA levels. In the presence of increasing T levels, SHBG levels fell to 39% of control values at 5 nM T (P = 0.047), rising to 97% of control at 500 nM. Conversely, incubation with EE2 produced a rise in SHBG secretion of more than 100% at 0.5 nM (P less than 0.02) which was sustained to 50 nM (P less than 0.005). DNA levels did not change with the addition of testosterone or EE2, with the exception of a 15% reduction at 5 nM EE2 (P less than 0.05). Albumin levels in the medium were not significantly altered by either steroid. However, in response to T, androgen receptor (AR) levels were reduced in cytosolic (42% of control) and nuclear (22%) fractions at 5 nM, and these changes in ARc and ARn correlated with SHBG levels over the range of T concentrations (P = 0.04 and P = 0.017, respectively). Nuclear estrogen receptor (ER) increased over 10-fold at 5 and 50 pM EE2 (P less than 0.001) and maintained 50 nM (P less than 0.001). Cytosolic ER was reduced at 0.5 and 5 nM but recovered at 50 nM, correlating with SHBG levels (P less than 0.001). These findings are consistent with the hypothesis that estrogens and androgens regulate SHBG synthesis in man by direct, specific, probably receptor-mediated effects on hepatocytes. Hep G2 cells grown in serum-free medium are a suitable experimental system for further study of this phenomenon.
J Steroid Biochem Mol Biol 1990 Dec 10
PMID:Estrogen and androgen regulation of sex hormone binding globulin secretion by a human liver cell line. 227 57

A series of simian virus 40 (SV40)-immortalized hepatocyte cell lines were characterized for albumin production, the regulation of albumin production, and the expression of other liver-specific genes. This series of cell lines is particularly useful for studying the regulation of hepatocyte gene expression because the cell lines express liverlike levels of a number of liver-specific functions and do so while growing in a chemically defined medium. SV40-immortalized hepatocyte cell lines were derived from colonies of albumin-producing epithelial cells that arose after primary hepatocytes maintained in chemically defined medium were transfected with SV40 DNA. Some cell lines secreted albumin at levels equal to or greater than those secreted by freshly plated primary hepatocytes, and all but one line continued to produce albumin for more than 20 passages. The variation in albumin secretion among cell lines reflected differences in the amount of albumin produced per cell and not in the percentage of albumin-producing cells in each line. The characterization of selected cell lines showed that albumin production was regulated by cell density during the growth cycle. Albumin production in most cell lines was also regulated by dexamethasone; however, one cell line continued to produce high levels of albumin when the cells were grown in medium lacking dexamethasone, demonstrating that although glucocorticoid can induce albumin production in some cell lines, it is not required for high levels of albumin production by all cells in culture. Regulation of albumin production measured at the level of protein secretion was paralleled by changes in steady-state levels of a 2.3-kilobase albumin RNA. Albumin-producing SV40-immortalized hepatocytes secreted a variety of other plasma proteins, including transferrin, hemopexin, and the third component of complement. These cells also expressed tyrosine aminotransferase activity that was inducible by dexamethasone. Alpha-fetoprotein production was not detected in any of the cell lines examined.
Mol Cell Biol 1987 Oct
PMID:Regulation of albumin gene expression in a series of rat hepatocyte cell lines immortalized by simian virus 40 and maintained in chemically defined medium. 244 20

We conducted the present study in an attempt to correlate function with the rate of molecular evolution for serum albumin and alpha-fetoprotein. We found a high rate of silent substitution (between 5 X 10(-9) and 7 X 10(-9)/site/year) for both the albumin and alpha-fetoprotein genes, perhaps the highest so far reported for an expressed nuclear gene. The rates of effective substitution and amino acid changes were also very high, but in contrast to silent substitutions, they are higher for alpha-fetoprotein than for albumin by approximately 70%. For alpha-fetoprotein, the rate of effective substitution (1.5 X 10(-9)/site/year) may be approaching that for nonfunctional pseudogenes (about 3 X 10(-9)/site/year). Evolutionary divergence was also estimated at the amino acid level. It was found that the rate of change of alpha-fetoprotein (55% amino acids replaced in 100 Myr) approaches that of the fastest-evolving fibrinopeptides (92% amino acids replaced in 100 Myr). This high rate may indicate that alpha-fetoprotein can tolerate a great deal of molecular variation without its function being impaired in the process. Albumin evolves at a slower rate (39% amino acids replaced in 100 Myr), although still faster than either hemoglobin (17% amino acids replaced in 100 Myr) or cytochrome c (5% amino acids replaced in 100 Myr). The slower evolutionary rate may indicate that albumin has more refined functional specifications and hence can tolerate fewer mutational changes. The latter conclusion remains, however, to be reconciled with the condition of inherited analbuminemia, where a virtually complete absence of albumin produces surprisingly few symptoms.
Mol Biol Evol 1985 Jul
PMID:The rate of molecular evolution of alpha-fetoprotein approaches that of pseudogenes. 245 56

The present study examined 1) whether the estrogen-regulated destabilization of albumin mRNA occurs in the nuclear or extranuclear fraction of the liver cell, and 2) whether the selective posttranscriptional regulation of albumin mRNA stability might result from covalent changes introduced in the processing or polyadenylation of the primary transcript. The disappearance of albumin mRNA after estrogen is restricted to the extranuclear fraction of the cell. Transient changes in steady state levels of the mature nuclear transcript were observed that mirrored the transient estrogen-induced changes previously reported for albumin gene transcription. When assayed 24 h after estrogen (when albumin RNA is virtually undetectable in the extranuclear fraction) the steady state levels of both the primary and mature albumin transcripts found in the nucleus were the same as observed in control animals. Estrogen had no effect on the splicing or selection of polyadenylation sites on the 3'-UTR as determined by high resolution gel analysis of the 3'-UTR and DNA sequencing of cDNA clones isolated from a liver library from an estrogen-treated male Xenopus. Most eukaryotic mRNAs have poly(A) tracts several hundred residues in length, and recent studies have demonstrated that a change in the stability of a number of mRNAs correlates directly with the degree of polyadenylation. Albumin contrasts sharply with this, first because it has an exceptionally short poly(A) tail of 17 residues, and second because the degree of polyadenylation is totally unrelated to its destabilization in response to estrogen. These findings indicate that a unique pathway is involved in the regulation of albumin RNA stability by estrogen in Xenopus.
Mol Endocrinol 1989 May
PMID:Extranuclear estrogen-regulated destabilization of Xenopus laevis serum albumin mRNA. 254 54


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