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1.
Panin LE Tuzikov FV Gimautdinova OI 《The Journal of steroid biochemistry and molecular biology》2003,87(4-5):309-318
Tetrahydrocortisol stimulates DNA and protein biosynthesis in hepatocytes only when it enters the complex with apolipoprotein A-I. Tetrahydrocortisol–apolipoprotein A-I (THC–apoA-I) complex specifically interacts with eukaryotic DNA isolated from rat liver. In the process of interaction, rupture of hydrogen bonds between the pairs of nitrous bases occurs with the formation of single-stranded DNA structures. In such state DNA forms complexes with DNA-dependent RNA-polymerase. The most probable site of binding the tetrahydrocortisol–apolipoprotein A-I complex with DNA is the sequence of CC(GCC)n type entering the structure of many genes, among them the structure of human apolipoprotein A-I gene. Oligonucleotide of this type has been synthesized. Association constant (Kass) of it with tetrahydrocortisol–apolipoprotein A-I complex was shown to be 1.66×106 M−1. Substitution of tetrahydrocortisol for cortisol in the complex results in a considerable decrease of Kass. It was assumed that in the GC-pairs of the given sequence tetrahydrocortisol itself participates in the formation of hydrogen bonds with cytosine, favoring their rupture with complementary base—guanine. 相似文献
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Panin LE Maksimov VF Usynin IF Korostyshevskaya IM 《The Journal of steroid biochemistry and molecular biology》2002,81(1):69-76
A novel mechanism of protein biosynthesis regulation in liver under the action of reduced forms of steroid hormones (tetrahydrocortisol) and apolipoprotein A-I (apoA-I) is presented. Kupffer cells play an important role in uptake of the cortisol and high density lipoproteins (HDL) as well as in formation of the active complex, tetrahydrocortisol+apolipoprotein A-I (THC-apoA-I). If macrophages are stimulated by lipopolysaccharides (LPS), these processes enhance dramatically, thus causing parallel activation of nucleolar DNA expression and ribosome formation in hepatocytes. THC-apoA-I complex accelerates protein biosynthesis in primary cultures of hepatocytes, but not in macrophages and endotheliocytes. 相似文献
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Panin LE Tuzikov FV Tuzikova NA Usynin IF Gimautdinova OI 《Bioorganicheskaia khimiia》2001,27(2):114-119
A mechanism of activation of protein biosynthesis in hepatocytes was proposed as effected by the conditioned medium of nonparenchymal liver cells incubated in the presence of high density lypoproteins, cortisol, and lypopolysaccharides. It was found that the increase in the biosynthesis rate was associated with the formation of the tetrahydrocortisol-apolipoprotein A-I (THC-apoA-I) complex in macrophages, which display 5 alpha- and 5 beta-reductase activity and are constituents of nonparenchymal liver hepatocytes. Using the small-angle X-ray scattering technique, it was shown that the THC-apoA-I-eukaryotic DNA interaction may break hydrogen bonds between pairs of complementary nucleic bases and cause the formation of single-stranded DNA fragments capable of binding to DNA-dependent RNA polymerase. The interaction is highly cooperative and has a saturating mode, up to six enzyme molecules being bound per DNA molecule. 相似文献
5.
Panin L. E. Tuzikov F. V. Tuzikova N. A. Usynin I. F. Gimautdinova O. I. 《Russian Journal of Bioorganic Chemistry》2001,27(2):95-100
A mechanism of activation of protein biosynthesis in hepatocytes was proposed as effected by the conditioned medium of nonparenchymal liver cells incubated in the presence of high density lipoproteins, cortisol, and lipopolysaccharides. It was found that the increase in the biosynthesis rate was associated with the formation of the tetrahydrocortisol–apolipoprotein A-I (THC–apoA-I) complex in macrophages, which display 5- and 5-reductase activity and are constituents of nonparenchymal liver cell. Using the small-angle X-ray scattering technique, it was shown that the THC–apoA-I–eukaryotic DNA interaction may break hydrogen bonds between pairs of complementary nucleic bases and cause the formation of single-stranded DNA fragments capable of binding to DNA-dependent RNA polymerase. The interaction is highly cooperative and has a saturating mode, up to six enzyme molecules being bound per DNA molecule. 相似文献
6.
An IR-spectroscopy study of the mechanism of interaction between duplex CC(GCC)5/GG (CGG)5Li2 and tetrahydrocortisol or tetrahydrocortisol-apolipoprotein A-I complex revealed the formation of hydrogen bonds between the OH group of the tetrahydrocortisol A-ring and the C=0 group of cytosine or guanine. Tetrahydrocortisol forms hydrogen bonds with the PO2-group of the duplex and with the OH-group of monosaccharide. The interaction of tetrahydrocortisol and apolipoprotein A-I with the duplex occurs at the same active site, namely, with the C=O-group of bases. The order --> order structural transition takes place in the duplex under the action of tetrahydrocortisol. The order --> disorder structural transition takes place in the duplex under the action of tetrahydrocortisol-apolipoprotein A-I complex. 相似文献
7.
Panin LE Tuzikov FV Tuzikova NA Gimautdinova OI Poliakov LM 《Molekuliarnaia biologiia》2002,36(1):96-102
The complex formed by tetrahydrocortisol (THC) and apolipoprotein A-I (ApoAI) specifically interacts with eukaryotic DNA from rat liver. Taken together, physical and chemical data and the results of small-angle X-ray scattering analysis show that interaction of the THC-ApoAI complex with eukaryotic DNA results in deformation of the DNA double helix. Single-stranded fragments were demonstrated to cause deformation of the double helix. In this state DNA forms complexes with DNA-dependent RNA polymerase. This interaction is cooperative and of saturating type; up to six enzyme molecules bind with one DNA molecule. The putative site of complex binding with DNA is the sequence CC(GCC)n found in many genes including the human ApoAI gene. An oligonucleotide of this type was synthesized. Its association constant (Ka) was 1.66 x 10(6) M-1. Substitution of THC with cortysol considerably decreases the Ka. We suggest that THC interacting with GC pairs of the binding site forms hydrogen bonds with cytosine, inducing rupture of the bonds within the complementary nucleic base pair. 相似文献
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P. V. Mokrushnikov A. N. Dudarev T. A. Tkachenko A. Y. Gorodetskaya I. F. Usynin 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2017,11(1):48-53
Using a pyrene as a fluorescent probe, we investigated the influence of native and oxidized apolipoprotein A-I (apo A-I) and their complexes with tetrahydrocortisol (THC) on the microviscosity of the erythrocyte plasma membrane. The addition of THC to isolated membranes led to a 17% increase in the membrane microviscosity. In contrast, native apo A-I reduced the microviscosity (i.e., increased the fluidity) of the membranes by 15%. A more pronounced increase (by 25%) in the membrane fluidity was found in the presence of the complex of apo A-I with THC. Unlike native apo A-I, oxidized apo A-I and its complex with THC did not change the membrane viscosity. In view of the fact that apo A-I plays an important role in the binding of membrane cholesterol we suggest that the observed increase in the membrane fluidity under the influence of the native apo A-I is associated with the cholesterol efflux from plasma membrane. Oxidative modification of apo A-I likely disturbs the mechanisms of the cholesterol efflux and prevents the decrease in the membrane microviscosity. 相似文献
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Immune-regulation of the apolipoprotein A-I/C-III/A-IV gene cluster in experimental inflammation 总被引:3,自引:0,他引:3
Navarro MA Carpintero R Acín S Arbonés-Mainar JM Calleja L Carnicer R Surra JC Guzmán-García MA González-Ramón N Iturralde M Lampreave F Piñeiro A Osada J 《Cytokine》2005,31(1):52-63
Apolipoprotein A-IV is a member of the apo A-I/C-III/A-IV gene cluster. In order to investigate its hypothetical coordinated regulation, an acute phase was induced in pigs by turpentine oil injection. The hepatic expression of the gene cluster as well as the plasma levels of apolipoproteins were monitored at different time periods. Furthermore, the involvement of the inflammatory mediators' interleukins 1 and 6 and tumor necrosis factor in the regulation of this gene cluster was tested in cultured pig hepatocytes, incubated with those mediators and apo A-I/C-III/A-IV gene cluster expression at the mRNA level was measured. In response to turpentine oil-induced inflammation, a decreased hepatic apo A-IV mRNA expression was observed (independent of apo A-I and apo C-III mRNA) not correlating with the plasma protein levels. The distribution of plasma apo A-IV experienced a shift from HDL to larger particles. In contrast, the changes in apo A-I and apo C-III mRNA were reflected in their corresponding plasma levels. Addition of cytokines to cultured pig hepatocytes also decreased apo A-IV and apo A-I mRNA levels. All these results show that the down-regulation of apolipoprotein A-I and A-IV messages in the liver may be mediated by interleukin 6 and TNF-alpha. The well-known HDL decrease found in many different acute-phase responses also appears in the pig due to the decreased expression of apolipoprotein A-I and the enlargement of the apolipoprotein A-IV-containing HDL. 相似文献
12.
Marke E. Swanson Thomas E. Hughes Irene St Denny Dennis S. France James R. Paterniti Jr Carlo Tapparelli Patrick Gfeller Kurt Bürki 《Transgenic research》1992,1(3):142-147
To examine the consequences of increased apolipoprotein A-I production on cholesterol and lipoprotein metabolism, we have
produced two lines of transgenic rats; one expressing moderate and one very high levels of human apolipoprotein A-I. The rats
were produced by microinjection of a 13 kbp DNA fragment containing the human apolipoprotein A-I gene plus 10 kbp of its 5′
flanking sequence and 1 kbp of its 3′ flanking sequence. Both lines of transgenic rats express human apolipoprotein A-I mRNA
in liver and human apolipoprotein A-I in plasma. Sera from these rats contain significantly higher levels of total apolipoprotein
A-I, high density lipoprotein cholesterol and phospholipid than sera from non-transgenic littermates. Transgenic rats expressing
high levels of human apolipoprotein A-I have reduced levels of serum rat apolipoprotein A-I suggesting a mechanism exists
to down-regulate apolipoprotein A-I production. These transgenic rats provide a unique animal model to examine the effects
of increased apolipoprotein A-I production on lipid and lipoprotein metabolism. 相似文献
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Hepatic lipocytes, the retinoid-storing cells of the liver, share several characteristics with vascular smooth muscle cells. To determine whether they also share the characteristic of apolipoprotein E secretion, we have compared the relative mRNA expression and protein secretion of apolipoprotein E, apolipoprotein A-I, and apolipoprotein A-IV in early primary cultures of lipocytes, hepatocytes, and Kupffer cells. Expression of apolipoprotein mRNAs was detected using the polymerase chain reaction and oligonucleotide primers specific for apolipoprotein E, apolipoprotein A-I, and apolipoprotein A-IV. Cellular mRNA concentrations were compared by dot blot analysis, and apolipoprotein secretion was assessed by immunoblot analysis of culture media. Apolipoprotein E mRNA was found in all three cell types, whereas apolipoprotein A-I and A-IV mRNAs were detected only in hepatocytes. Hepatocyte, lipocyte, and Kupffer cell media all contained a Mr approximately 36,000 protein identified by an antibody specific for rat apolipoprotein E. The relative concentration of apolipoprotein E mRNA per microgram of total cellular RNA in lipocytes, hepatocytes, and Kupffer cells was 1.0, 3.0, and 1.6, respectively. The relative secretion of apolipoprotein E per cell was also lowest in lipocytes, being twofold greater in hepatocytes and 1.4-fold greater in Kupffer cells. The secretion of apolipoprotein E by lipocytes is not only an additional smooth muscle cell-like characteristic of the hepatic lipocyte, but also raises the possibility of retinol mobilization upon apolipoprotein secretion. 相似文献
15.
Panin L. E. Tuzikov F. V. Tuzikova N. A. Gimautdinova O. I. Polyakov L. M. 《Molecular Biology》2002,36(1):76-81
The complex formed by tetrahydrocortisol (THC) and apolipoprotein A-I (ApoAI) specifically interacts with eukaryotic DNA from rat liver. Taken together, physical and chemical data and the results of small-angle X-ray scattering analysis show that interaction of the THC–ApoAI complex with eukaryotic DNA results in deformation of the DNA double helix. Single-stranded fragments were demonstrated to cause deformation of the double helix. In this state DNA forms complexes with DNA-dependent RNA polymerase. This interaction is cooperative and of saturating type; up to six enzyme molecules bind with one DNA molecule. The putative site of complex binding with DNA is the sequence CC(GCC)n found in many genes including the human ApoAI gene. An oligonucleotide of this type was synthesized. Its association constant (K
a) was 1.66·106 M–1. Substitution of THC with cortisol considerably decreases the K
a. We suggest that THC interacting with GC pairs of the binding site forms hydrogen bonds with cytosine, inducing rupture of the bonds within the complementary nucleic base pair. 相似文献
16.
W L Blake T J Vidmar G W Melchior 《Biochemical and biophysical research communications》1992,186(1):199-204
EGF has been shown to augment albumin and apolipoprotein A-I secretion by cynomolgus monkey hepatocytes in primary culture without stimulating cell division. This study was undertaken to determine what effect EGF had on apo B secretion by those hepatocytes. The results indicate that EGF (3 nM final concentration) severely inhibits the rate at which apo B accumulates in the culture medium of primate hepatocytes. That effect was evident within 48 hours of treatment, and by 72 hours the rate that apo B accumulated was less than half that of cells treated with a hormone-free medium. However, the apo B mRNA levels in the EGF-treated cells were more than double those of hepatocytes given the hormone-free medium. These data indicate that EGF has a potent effect on the rate at which apo B accumulates in the culture medium of primate hepatocytes and that the effect is independent of apo B gene expression. 相似文献
17.
N Karásková K Bezouska L Stárka R Hampl O Tàborsky 《Biokhimii?a (Moscow, Russia)》1987,52(10):1677-1682
The effect of desialation of human transcortin on the transcortin-cortisol complex transport into hepatocytes and on subsequent intracellular distribution of the complex components was studied in model experiments with perfused rat liver. It was demonstrated that in the presence of desialated transcortin the time of [3H]cortisol incubation in the perfusion medium decreased more than 200 times as compared with the native protein. [3H]cortisol and [131I]asialotranscortin trapping by hepatocytes occurs simultaneously. The content of the [3H]cortisol--[131I]asialotranscortin complex in rat liver plasma membranes reaches a maximum 3 min after beginning of perfusion. Then the intact complex is transported into lysosomes, where it dissociates with a subsequent release of asialotranscortin and cortisol metabolites into the cytoplasm. 相似文献
18.
L. E. Panin O. I. Gimautdinova P. A. Kuznetsov E. Ju. Velichko V. V. Bazaluk 《Molecular Biology》2007,41(4):583-588
High affinity for DNA and synthetic oligonucleotides was detected for apolipoprotein A-I (ApoA-I) by affinity chromatography, affinity modification, and enzymatic analysis. Competitive inhibition and Southern hybridization showed that the tetrahydrocortisol (THC)-ApoA-I complex specifically bound to high-molecular-weight DNA in regions containing GCC/CGG sequences. The CC(GCC)3 · GG(CGG)3 duplex was found to be sensitive to nuclease S1 under the action of the THC-ApoA-I complex. The eukaryotic DNA binding sites for steroid (THC, androsterone)-ApoA-I complexes were found to be involved in the initiation of DNA copying in vitro. 相似文献
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Changes in apolipoprotein A-I mRNA level in the liver of rats with experimental nephrotic syndrome 总被引:1,自引:0,他引:1
In previous studies we had shown that: one of the most specific feature of hyperlipoproteinemia found in rats with experimental nephrotic syndrome is the accumulation of apolipoprotein A-I-rich HDL in plasma and this disorder is associated with an overproduction of apolipoprotein A-I by the liver. The present study was designed to investigate whether the increased hepatic synthesis of apolipoprotein A-I was due to an accumulation of functionally active apolipoprotein A-I mRNA in liver of nephrotic rats. Hepatic mRNA was translated in vitro by rabbit reticulocyte lysate in the presence of [35S]methionine and in vitro synthesized apolipoprotein A-I, albumin and apolipoprotein E were immunoprecipitated by specific rabbit IgG. In nephrotic rats the amount of in vitro synthesized apolipoprotein A-I was almost twice that found in the controls, suggesting that functionally active apolipoprotein A-I mRNA was increased in liver of nephrotic rats. To confirm that this difference in apolipoprotein A-I mRNA activity was due to an actual increase of hepatic apolipoprotein A-I mRNA sequences, we performed nucleic acid hybridization experiments (northern blot) using several cloned cDNA probes (rat and human apolipoprotein A-I, rat apolipoprotein E and apolipoprotein A-II). The results indicate that in nephrotic rats the amount of hybridizable apolipoprotein A-I mRNA sequences was about 3-fold higher than that in controls. In contrast, there was no difference in the amount of hybridizable apolipoprotein A-II and apolipoprotein E mRNA sequences, indicating that the change in apolipoprotein A-I mRNA induced by the nephrotic state was specific for this mRNA. 相似文献