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Query: UNIPROT:P06889 (Mol)
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Two sheep with a ruminal fistula and an isolated small rumen were studied for the secretion of ammonia nitrogen, urea nitrogen, and amino nitrogen into the isolated rumen at different levels of volatile fatty acids (VFA) (50, 133-97, and 97-66 M Mol 1(-1)) in the rumen. The VFA level in the rumen was found to exert a great influence on the quantitative secretion of endogenous nitrogen from the blood through the rumen wall into rumen content. When the VFA level in the rumen was increased by administration of a single dose of acetic, propionic, and butyric acid, the secretion of ammonia nitrogen and amino nitrogen abruptly dropped and the secretion of urea into the isolated rumen slightly increased. The over-all amount of nitrogen (NH3-N + urea-N + amino-N) that had passed into the isolated rumen in the course of an hour showed a highly significant correlation with the passage of nitrogen in the form of ammonia and amino nitrogen and was greatest before the application of VFA to the rumen, i.e. at the level of 50 m mol 1-1. Of the metabolites under study, which were passing to the isolated rumen, amino nitrogen shared the greatest proportion (45.38-46.54%). When the VFA level in the rumen was raised, the proportion of ammonia secreted to the isolated rumen decreased and the proportion of urea in the total amount of nitrogen increased.
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PMID:[Relationship between the volatile fatty acids (VFA) in the rumen and nitrogen secretion into isolated sheep's rumen]. 41 43

47 types of green feeds and roughages were subjected to an in-vitro fermentation with dilute ruminal fluid. The volatile fatty acids produced in this process were determined quantitatively in accordance with the method of digestibility estimation proposed by Tilley and Terry (1963). An average of 5 Mol FFS (FFS=volatile fatty acids) was found per kg of dried feed, a value is also reported in the literature. The ratios of acetate to propionate to n-butyrate to iso-butyrate to n-valerianate were 64.2 : 25.4 : 6.6 : 0.8 : 1.5 : 1.5. In this ratio, propionic acid predominated so that acetic acid and n-butyric acid were misrepresented compared with the data of in-vivo measurements made for the corresponding foodstuffs. Consequently, it is only within certain limits that values of FFS concentrations obtained in vitro may be used for estimating net energy data, disregardful of the fact that the FFS are the main source of metabolizable energy in ruminants. The reliability index for an estimation of Starch Equivalents and NEFr based on the above-mentioned method was found to be considerable lower (0.71 and 0.80) than that based on in-vitro digestibility measurements (0.86).
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PMID:[Estimation of the net energy using volatile acids produced in the process of in-vitro digestion with ruminal fluid]. 86 14

Three non-lactating cows (Deutsches Schwarzbuntes Rind) with large ruminal fistulas were fed coarsely structured food. Within a trial period of 21 weeks infusion periods lasting 3 weeks alternated with equally long control periods (K). During the 3 infusion periods, 8.4 mMol of propionic acid (P), 14.8 mMol of acetic acid (E) and 4,5 mMol of butyric acid (B) per kg liveweight per day were administered through the fistula, the total quantity being 19 litres of solution. In the periods K1...4 the ruminal fluid contained an average of 68 Mol% E, 19 Mol% P, 13 Mol% B (maximum of 10.25 mMol free fatty acids (FFS) per 100 ml, minimum pH 6.4). In the course of the 10 hrs of infusion the Mol percentages of the particular acids infused increased to 27% P (maximum of 11.14 mMol FFS per 100 ml, minimum pH 6.4) or 79% E (maximum of 12,99 mMol FFS per 100 ml, minimum pH 6.0 (5.5)) or 25% B (maximum of 10.34 mMol FFS per 100 ml, minimum pH 6.0 (5.5)). Infusions of E and B had the most pronounced effect on the ruminal mucosa compared with the K periods. All fatty acids increased the process of keratinization and decreased the size of cell nuclei in the stratum basale. As specific effect, P infusions produced a thickening of the lamina propria; B infusions caused a thickening of the stratum germinativum (proliferative effect) while e infusions led to a drastically reduced thickness of villi (antiproliferative effect) due to reductions in the stratum germinativum and the lamina propria. According to the morphological situation high specific mucosal function is suggested during the B-period. The mucosa appeared quite normal during all periods investigated, with the exception of the E period, where hyperkeratosis, atrophy and necrosis were observed in 34% of the sample. Changes in the state of the mucosa appeared as early as 1 week after the beginning of the respective trial periods. Keratin consolidation was the primary cause for chemically induced keratosis. The development of hyperkeratosis seemed to be favoured if low pH values occurred in the rumen in combination with small amounts of metabolites inducing proliferation, both representing synergistic factors.
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PMID:[The effect of nutritional factors on the ruminal mucosa. 3. Condition of the mucosa after infusion of propionic acid, acetic acid and butyric acid]. 87 Dec 52

We have studied the effects of sodium butyrate on cell morphology and the expression of mRNAs encoding voltage-gated sodium channels in five neuronal cell lines, B35, B50, B65, B103 and B104, all derived from the rat CNS. The cells were grown in medium supplemented with 2.5 mM sodium-n-butyrate and examined daily by phase-contrast microscopy. Sodium butyrate caused slowing of cell division and the formation of longer and more highly branched cytoplasmic processes than were present in untreated cells. Expression of sodium channel mRNA was analysed by PCR with primers that allow the transcripts encoding the different types of sodium channel to be distinguished according to the lengths of the PCR products. The identity of the PCR products was confirmed by restriction enzyme digestion. Southern blotting and hybridization with internal radiolabelled probes. Prior to sodium butyrate treatment, expression of sodium channel mRNA was largely restricted to B50 and B104 cells: B50 cells showed expression of rat brain types I and II sodium channel and B104 cells expressed rat brain type III sodium channel. After treatment for 5 days with sodium butyrate, sodium channel mRNA was detected in all five cell lines. In addition to type I and type II sodium channel, B50 cells expressed rat brain type III sodium channel. These three types of sodium channel were also expressed by B35, B65 and B103 cells. Even after butyrate treatment, B104 cells expressed only type III sodium channel. The treatment also induced expression of rat skeletal muscle SkM1 sodium channel in B35 cells but only trace amounts in the other neuronal cell lines.
Brain Res Mol Brain Res 1992 Dec
PMID:Effects of sodium butyrate on the expression of sodium channels by neuronal cell lines derived from the rat CNS. 128 97

Human pregnancy-specific glycoproteins (PSGs) are a family of closely related placental proteins that, together with the carcinoembryonic antigen members, comprise a subfamily within the immunoglobulin superfamily. To facilitate study of the control of PSG expression, we immortalized human placental cell lines with adenovirus-origin-minus (ori-)-simian virus-40 (SV40) recombinant viruses containing either wild-type or temperature-sensitive (ts) A mutants of SV40. Cells transformed with the SV40 tsA chimera (HP-A1 and HP-A2), but not the SV40 wild-type chimera (HP-W1), were temperature sensitive for transformation. All three cell lines expressed trophoblast-specific genes, including PSG and the alpha- and beta-subunits of hCG. Human CG alpha expression was greatly stimulated by (Bu)2cAMP in all three cell lines; shifting HP-A1 and HP-A2 cells to the nonpermissive temperature (39.5 C) further increased hCG alpha expression. At both 33 C (permissive temperature) and 39.5 C, the transformed placental cells expressed PSG mRNAs of 2.2 and 1.7 kilobases; expression was greatly stimulated by sodium butyrate. In the absence of an inducer, the three placental lines synthesized a PSG of 64 kilodaltons (kDa). In the presence of butyrate, they synthesized PSGs of 72, 64, and 54 kDa, similar to the placental PSGs. However, in placenta the predominant species is the 72-kDa product. At 39.5 C, butyrate selectively increased synthesis of the 72-kDa PSG in HP-A1 and HP-A2 cells. To characterize PSG promoter activity, we constructed chloramphenicol acetyltransferase (CAT) fusion genes containing -809 to -44 basepairs up-stream of the translational start site of the PSG6 gene. Using transient expression assays, we demonstrated that the -809/-44 region of the PSG6 gene contained cis-acting sequences that can direct CAT expression in human placental cells. Sodium butyrate, which stimulates PSG expression, greatly increased CAT activity, indicating that butyrate-induced PSG expression is regulated primarily at the level of gene transcription.
Mol Endocrinol 1992 May
PMID:Immortalization of virus-free human placental cells that express tissue-specific functions. 131 3

Sodium butyrate reversibly inhibits muscle differentiation and blocks the expression of many muscle-specific genes in both proliferating myoblasts and differentiated myotubes. We investigated the role of the basic helix-loop-helix (bHLH) myogenic determinator proteins MyoD and myogenin in this inhibition. Our data suggest that both MyoD and myogenin are not able to function as transcriptional activators in the presence of butyrate, although both apparently retain the ability to bind DNA. Transcription of MyoD itself is extinguished in butyrate-treated myoblasts and myotubes, an effect that may be due to the inability of MyoD to autoactivate its own transcription. We present evidence that the HLH region of MyoD is essential for butyrate inhibition of MyoD. In contrast to MyoD and myogenin, butyrate does not inhibit the ubiquitous basic HLH protein E2-5 from functioning as a transcriptional activator.
Mol Cell Biol 1992 Nov
PMID:Sodium butyrate inhibits myogenesis by interfering with the transcriptional activation function of MyoD and myogenin. 132 72

We previously demonstrated that 3'-azido-3'-deoxythymidine (AZT) inhibits hemoglobin (Hb) synthesis and globin gene transcription in butyric acid-induced K-562 leukemia cells, suggesting that these effects may play a role in the AZT-induced anemia observed in patients [Mol. Pharmacol. 38:797-804 (1990)]. The recent discovery by our group of a novel metabolite of AZT. 3'-amino-3'-deoxythymidine (AMT), which exhibits a high degree of toxicity toward human hemopoietic cells [Mol. Pharmacol. 39:258-266 (1991); Antimicrob. Agents Chemother. 35:801-807 (1991)], has led us to explore potential effects of this AZT metabolite on Hb production, globin mRNA expression, and heme synthesis in butyric acid-induced K-562 human erythroleukemia cells. AMT inhibited Hb synthesis by approximately 21%, as measured by benzidine staining, at concentrations as low as 25 microM, with slightly increased inhibition at higher AMT concentrations. The inhibition of Hb production by AMT was substantially lower, compared with that of AZT. AMT inhibited globin mRNA steady state levels in a dose-dependent manner to a similar extent as did the parent drug, with approximately 50% inhibition by each compound at a concentration of 100 microM. Nuclear run-on transcription assays demonstrated that inhibition by AMT of globin mRNA synthesis was associated with a decreased rate of globin-specific gene transcription. Globin mRNA stability was not affected by either 100 microM AZT or AMT, as measured after blockage of transcription with actinomycin D. To gain insight into potential mechanism(s) responsible for the different quantitative effects of AZT and AMT on Hb synthesis, the effect of each compound on induction of heme synthesis in K-562 cells was determined. Although heme induction was not affected by AMT, a significant inhibition approximating 20% was observed in the presence of 100 microM AZT. In addition, AZT down-regulated mRNA steady state levels under conditions where heme synthesis was inhibited by succinylacetone. These data suggest that inhibition by AZT of globin gene expression is a direct effect and is not secondary to inhibition of heme synthesis. This study emphasizes the role of AMT in the pharmacodynamic properties of AZT, in relation to its toxicity, and suggest that both AMT and AZT may be involved in the inhibition of erythroid differentiation observed in vivo, through changes in gene expression.
Mol Pharmacol 1992 Feb
PMID:Comparative effects of 3'-azido-3'-deoxythymidine and its metabolite 3'-amino-3'-deoxythymidine on hemoglobin synthesis in K-562 human leukemia cells. 153 5

A stable transfection assay was used to test the mechanism by which embryonic globin gene transcription is stimulated in adult erythroid cells exposed to butyric acid and its analogs. To test the appropriate expression and inducibility of chicken globin genes in murine erythroleukemia (MEL) cells, an adult chicken beta-globin gene construct was stably transfected. The chicken beta-globin gene was found to be coregulated with the endogenous adult mouse alpha-globin gene following induction of erythroid differentiation of the transfected MEL cells by incubation with either 2% dimethyl sulfoxide (DMSO) or 1 mM sodium butyrate (NaB). In contrast, a stably transfected embryonic chicken beta-type globin gene, rho, was downregulated during DMSO-induced MEL cell differentiation. However, incubation with NaB, which induces MEL cell differentiation, or alpha-amino butyrate, which does not induce differentiation of MEL cells, resulted in markedly increased levels of transcription from the stably transfected rho gene. Analysis of histone modification showed that induction of rho gene expression was not correlated with increased bulk histone acetylation. A region of 5'-flanking sequence extending from -569 to -725 bp upstream of the rho gene cap site was found to be required for both downregulation of rho gene expression during DMSO-induced differentiation and upregulation by treatment with NaB or alpha-amino butyrate. These data are support for a novel mechanism by which butyrate compounds can alter cellular gene expression through specific DNA sequences. The results reported here are also evidence that 5'-flanking sequences are involved in the suppression of embryonic globin gene expression in terminally differentiated adult erythroid cells.
Mol Cell Biol 1991 Sep
PMID:5'-flanking sequences mediate butyrate stimulation of embryonic globin gene expression in adult erythroid cells. 187 47

We previously demonstrated that 3'-azido-3'-deoxythymidine (AZT) inhibits proliferation of human bone marrow progenitor cells in vitro and that incorporation of AZT into nuclear DNA may be one mechanism responsible for AZT-induced bone marrow toxicity [Antimicrob. Agents Chemother. 31:452-454 (1987); Mol. Pharmacol. 36:9-14 (1989)]. The present study explores possible genetic mechanisms involved in AZT-induced anemia by evaluating the effects of AZT on globin gene expression at both the transcriptional and the translational levels in butyric acid-induced K-562 human erythroleukemia cells. AZT, at concentrations ranging from 10 to 250 microM, was added to cells 25 hr after initiation of induction of hemoglobin (Hb) synthesis with 1.4 mM butyric acid. Hb synthesis, as measured by benzidine staining, was inhibited by AZT in a dose- and time-dependent manner in these cells. AZT inhibition of cell growth was not the major contributing factor in the net inhibition of Hb synthesis in K-562 cells. As assessed by Northern blot analysis, AZT inhibition of Hb synthesis was associated with a decrease in globin mRNA steady state levels without inhibition of total RNA synthesis or actin mRNA steady state levels. In particular, a decrease of globin mRNA levels of 23% by 25 microM AZT was observed, reaching a maximum inhibition of 59% in the presence of 250 microM AZT. In vitro translation experiments demonstrated that essentially all nonglobin translatable mRNAs were not inhibited by AZT concentrations as high as 250 microM, whereas globin mRNAs coding for epsilon, zeta, A gamma, G gamma, and alpha chains were substantially inhibited to similar levels by AZT, in a dose-dependent manner. Transcriptional run-on studies with isolated nuclei from AZT-treated K-562 cells demonstrated a 20 and 50% inhibition of in vitro synthesized globin transcripts from cells exposed to 25 and 100 microM AZT, respectively. 2',3'-Dideoxycytidine also inhibited K-562 cell growth in the same concentration range as AZT but, of importance, had no effects on Hb production. These data suggest that inhibition of globin gene expression may play a role in the cytotoxicity of AZT to the erythroid cell.
Mol Pharmacol 1990 Dec
PMID:3'-Azido-3'-deoxythymidine inhibits globin gene transcription in butyric acid-induced K-562 human leukemia cells. 217 2

We describe experiments here which show that chemical esterification of 5'-adenylic acid (5'-AMP) with N-acetyl D- or L-phenylalanine (Ac-D- or Ac-L-Phe) imidazolide occurs principally, if not exclusively, at the 2' position. Furthermore, in experiments with the formation of the 2'-3' diester with butyric acid and N-acetyl glycine (Ac-Gly), we found the second esterification was also predominantly at the 2' position. This means that mixed diesters can be predictably prepared with the positions of the substituents known. The results are consistent with a model for the preferential catalytic synthesis of L-based peptides via a 2'-3' diester intermediate of purine monoribonucleotides.
J Mol Evol 1990 Oct
PMID:Chemical esterification of 5'-AMP occurs predominantly at the 2' position. 217 65


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