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S Tanuma

Publications and source records attributed to S Tanuma.

At least 55 records · Page 3Linked to original sources
PubMed1996

Inhibitory effect of tannic acid on human immunodeficiency virus promoter activity induced by 12-O-tetra decanoylphorbol-13-acetate in Jurkat T-cells.

We investigated the effect of tannic acid, a potent inhibitor of poly(ADP-ribose) glycohydrolase, on human viral gene transcription, by using chloramphenicol acetyl transferase (CAT) assay experiments transfecting Jurkat cells with CAT reporter constructs that contain the promoter region of human immunodeficiency virus (HIV) or of human T-cell leukemia virus type I (HTLV-1). The activity of HIV promoter induced by treatment with 12-O-tetradecanoylphorbol-13-acetate was suppressed by the addition of tannic acid. On the other hand, HTLV-1 promoter activity induced by the p40(tax) expression plasmid was not affected by tannic acid treatment. Deletion analysis of the HIV promoter revealed that a 30-bp element located immediately upstream of NF-kappa B motifs was responsible for the suppressive effect of tannic acid. This was supported by the observations that the negative effect of tannic acid was introduced to tannic acid-non-responsive thymidine kinase promoter by the insertion of this element 5'-upstream of the promoter.

Base Sequence↗
PubMed1995

A macrocircular ellagitannin, oenothein B, suppresses mouse mammary tumor gene expression via inhibition of poly(ADP-ribose) glycohydrolase.

Oenothein B, a macrocircular dimeric ellagitannin, was found to be a potent and specific inhibitor of poly(ADP-ribose) glycohydrolase. Oenothein B suppressed glucocorticoid-sensitive mouse mammary tumor virus (MMTV) transcription in 34I cells. This suppression was accompanied by inhibition of glucocorticoid-induced endogeneous de-poly(ADP-ribosyl)ation of high mobility group (HMG) 14 and 17 proteins. These results suggest that de-poly(ADP-ribosyl)ation of these proteins may be closely connected with the events initiating glucocorticoid-sensitive MMTV gene transcription.

Animals↗
PubMed1995

Induction of apoptosis by T-2 toxin and other natural toxins in HL-60 human promyelotic leukemia cells.

Based on the DNA fragmentation profile in gel electrophoresis and the morphological changes in electron microscopy, the induction of apoptotic nuclear changes by mycotoxins and other microbial products, in total 31 chemicals, was investigated in HL-60 human promyelotic leukemia cells, along with the cytotoxicity tests with 3-[4,5-dimethylthiazol-zyl]-2,5-diphenyltetrazolium bromide (MTT) and trypan blue exclusion. Among the chemicals tested, trichothecenes (T-2 toxin, roridin A, nivalenol, deoxynivalenol), certain anthraquinones (luteoskyrin, skyrin, 2-hydroxyemodin), diketopiperazines (emethallicin A, emestrin), isocoumarins (ochratoxin A, citrinin), lactone (penicillic acid), dihydrobisfuran (aflatoxin B1), potassium ionophore (valinomycin), and an inhibitor of interleukin-2 synthesis (cyclosporin A) were positive for the induction of DNA fragmentation. No DNA fragmentation was observed under the present conditions with fumonisin B1, cyclic peptides (cyclochlorotine, phalloidin, microcystin-LR), certain anthraquinones (emodin, chrysophanol, rugulosin), and others (sterigmatocystin, cytochalasin A, griseofulvin, fusaric acid, kojic acid, rubratoxin B, butenolide, wortmannin, FK506, and sphingosine). The apoptotic changes in the cells exposed to T-2 toxin and luteoskyrin were confirmed by electron microscopic observation. Detailed experiments on dose and time dependencies revealed that T-2 toxin induced the apoptosis at 10 ng/ml (= 4 x 10(-8) M) levels within 2-6 hr without significant cytotoxicity evaluated by the dye exclusion and MTT.

Anthraquinones↗
PubMed1995

Induction of autoantibodies in normal mice by injection of nucleobindin and natural occurrence of antibodies against nucleobindin in autoimmune MRL/lpr/lpr mice.

Our previous works have shown that nucleobindin (Nuc) or recombinant (r) Nuc not only augments anti-DNA antibody production in vitro but also accelerates autoimmune response in vivo in MRL/+/+ (MRL/n) mice which are the substrain of autoimmune MRL/lpr/lpr (MRL/l) mice. To investigate whether rNuc can induce autoimmune response similarly in naive mice, we carried out intraperitoneal (i.p.) injection of rNuc (5 micrograms) without adjuvant into 8-week-old female BALB/c mice and continued injection twice a week for 12 weeks. About 5 weeks after the first injection, all the mice began to show IgG hypergammaglobulinemia (HG) followed by elevation of a number of autoantibodies of the IgG class such as anti-double-stranded (ds) DNA, anti-U1 ribonuclear protein (RNP), anti-ssB(La) and anti-Fc antibodies (RF), but not by anti-Sm antibodies. However, the IgG anti-dsDNA antibody response and histopathological changes in the kidney of these BALB/c mice were not so noticeable as those in MRL/n mice induced by rNuc in our previous experiment. In contrast, the IgG anti-rNuc antibody response of normal BALB/c mice induced by rNuc was stronger than that of MRL/n mice induced by rNuc. Since the titers of each autoantibody of BALB/c mice induced by rNuc were not always associated with the level of IgG HG, and either IgG HG or IgG autoantibodies could not be induced by control administration of extracts (5 micrograms) of Escherichia coli with or without harboring plasmid alone, polyclonal B cell activation (PBA) appeared not to be the mechanism of this autoimmunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Apoptosis: its molecular mechanisms and biological roles].

Apoptosis is a mechanism for eliminating unwanted cells from the cell community of multicellular organisms. Abnormalities in the regulation of apoptosis may play a part in the aetiology of cancer, autoimmune diseases, AIDS, degenerative nerve diseases and malformation. On of the hallmarks of apoptosis is the enzymatic cleavage of genomic DNA into nucleosomal oligomers. The identification of an endonuclease responsible for apoptosis might help to explain how this cell suicide is regulated and why DNA is cleaved. Here, we found that gamma type of DNase was retained in apoptotic rat thymocyte nuclei. The mode of DNA cleavage, 3'-hydroxyl (OH)/5'-phosphoryl (P) ends, by homogeneously purified DNase gamma (Mr = 33 kDa) and its Zn2+ sensitivity match those observed in apoptosis in thymocytes induced by irradiation or glucocorticoid treatment, indicating that this endonuclease is a central component of the thymic apoptosis machinery.

Animals↗
PubMed1994

Identification of an endonuclease responsible for apoptosis in rat thymocytes.

Analyses of cleavage ends of DNA fragments in apoptotic rat thymocytes induced by gamma-ray irradiation or by treatment with dexamethasone revealed that in both cases the fragments produced had 3'-hydroxyl (OH) and 5'-phosphoryl (P) ends of DNA chains. Rat thymocyte nuclei contained at least three endonuclease activities (deoxyribonucleases alpha, beta and gamma) that were able to cleave chromatin to mononucleosomal and oligonucleosomal fragments. The nuclei of apoptotic rat thymocytes induced by gamma-ray irradiation or dexamethasone retained considerable deoxyribonuclease gamma activity, but not alpha or beta deoxyribonuclease activity. During the induction of apoptosis, treatment with cycloheximide, which suppressed apoptosis, resulted in marked decreases of deoxyribonucleases alpha and beta activities. After release of cycloheximide inhibition, DNA fragmentation associated with apoptosis occurred in the cycloheximide-treated thymocyte nuclei, in which deoxyribonuclease gamma activity was only observed. The purified deoxyribonucleases alpha and beta were divalent cation-independent acidic endonucleases, which were separated on a CM5PW column by HPLC. The molecular masses of deoxyribonucleases alpha and beta were 28 kDa and 30 kDa, respectively, as determined by TSK G-2000SW gel-filtration HPLC, and both were 32 kDa in molecular mass as determined by SDS/PAGE. In contrast, deoxyribonuclease gamma, a neutral endonuclease, required both Ca2+ and Mg2+ for full activity and was inhibited by Zn2+. The molecular mass of deoxyribonuclease gamma was 31 kDa and 33 kDa when measured by gel filtration and SDS/PAGE, respectively. Under these optimal conditions, deoxyribonuclease gamma was shown to produce 3'-OH/5'-P ends of nucleosomal DNA fragments, while deoxyribonucleases alpha and beta both formed DNA fragments with 3'-P/5'-OH ends. The ends formed by cleavage with deoxyribonuclease gamma were the same as those produced in apoptotic rat thymocytes. On the basis of these results, it seems likely that deoxyribonuclease gamma is responsible for internucleosomal cleavage of chromatin during thymic apoptosis.

Animals↗
PubMed1994

Multiple forms of nuclear deoxyribonuclease in rat thymocytes.

Three distinct endonucleases (DNase alpha, beta and gamma) were isolated from rat thymocyte nuclei. These three DNases differed in chromatographic behaviors and in apparent molecular masses. The cognate form of acidic DNases alpha and beta did not require divalent cations for their activities, whereas DNase gamma was a neutral endonuclease that required both Ca2+ and Mg2+ for full activity and was inhibited by Zn2+. These enzymes digested HeLa S3 cell nuclear chromatin to the nucleosomal fragments characteristic of apoptosis. Interestingly, apoptotic rat thymocyte nuclei induced by gamma-ray irradiation or glucocorticoid retained considerable activity of DNase gamma, whereas their activities of DNases alpha and beta were markedly reduced. These results indicate that in rat thymocytes DNase gamma is involved in DNA fragmentation during apoptosis.

Animals↗
PubMed1994

A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells.

Protein kinase C (PKC)-related cDNA clones isolated from cDNA libraries of mouse P19 embryonal carcinoma cells and mouse brain encoded a 67-kDa protein, PKC lambda. PKC lambda shows the highest amino acid sequence identity with PKC zeta (72%), the third class of the PKC family. Northern blot analysis showed that the mRNA for PKC lambda is expressed in a wide variety of cells and tissues, including P19 and NIH 3T3 cells, as well as brain, kidney, testis, and ovary. In undifferentiated P19 cells, the mRNA for PKC lambda is the most abundant among all the PKC family members. The differentiation of P19 cells results in an increase in PKC alpha and epsilon, and a decrease in PKC lambda. Antiserum raised against a peptide of PKC lambda identified a 74-kDa protein in P19 cell extracts as well as in extracts from COS cells transfected with the PKC lambda expression plasmid. Autophosphorylation of the PKC lambda that immunoprecipitated with the specific antiserum was observed, indicating that PKC lambda possesses protein kinase activity. A phorbol ester binding assay using intact COS cells expressing PKC lambda failed to detect binding activity specific to PKC lambda at phorbol dibutylate concentrations up to 300 nM, suggesting that PKC lambda does not possess phorbol ester binding activity. These results, in conjunction with the results obtained in parallel experiments with PKC zeta and other PKC members, suggest a biochemical similarity between PKC lambda and zeta and their clear difference from other PKC members.

Amino Acid Sequence↗
PubMed1993

Natural occurrence of Nuc in the sera of autoimmune-prone MRL/lpr mice.

We previously established a clone of cells termed KML1-7 which produces a soluble factor that boosts anti-DNA antibody production both in vitro and in vivo across the H-2 barrier. By using the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced recombinant(r) Nuc in E.coli. Although the purified rNuc showed biological activities such as anti-DNA antibody boosting and DNA binding, there was no evidence that Nuc is really associated with autoimmune status in lupus-prone MRL/lpr mice. Here we report that identification of Nuc was successful from the sera of MRL/lpr mice, but not from those of the substrain MRL/n mice, which show no apparent autoimmune syndrome at the same age of MRL/lpr mice, by means of immunochemical as well as N-terminal amino-acid sequencing methods.

Amino Acid Sequence↗
PubMed1993

Benzylideneascorbate induces apoptosis in L929 tumor cells.

Sodium 5,6-benzylideneascorbate (SBA), which is known to be an antitumor substance, was found to induce apoptotic cell death of L929 tumor cells directly in a concentration- and time-dependent manner. The dying cells exhibited cell shrinkage, disappearance of cell surface microvilli, chromatin condensation and DNA fragmentation into nucleosomal oligomers characteristic of apoptosis. These results indicate a possible mechanism by which SBA induces tumor regression in vivo.

Animals↗
PubMed1993

Preferential degradation of protein-bound (ADP-ribose)n by nuclear poly(ADP-ribose) glycohydrolase from human placenta.

Poly(ADP-ribose) glycohydrolase, extensively purified to homogeneity from nuclei of human placenta, is composed of a single polypeptide with a molecular mass of 71,000 daltons on sodium dodecyl sulfate-polyacrylamide gel. Judging from its physico-chemical and catalytic properties, the enzyme is similar to the nuclear glycohydrolase (glycohydrolase I), but not to the cytoplasmic glycohydrolase (glycohydrolase II) that has been purified from guinea pig liver (Tanuma, S., Kawashima, K., and Endo, H. (1986) J. Biol. Chem. 261, 965-969; Maruta, H., Inageda, K., Aoki, T., Nishina, H., and Tanuma, S. (1991) Biochemistry 30, 5907-5912). The rates of hydrolysis of (ADP-ribose)n bound to various proteins by the purified nuclear glycohydrolase were higher than those of the corresponding free polymers. Kinetic analyses revealed that the enzyme had more activity toward poly(ADP-ribose) bound to histone H1 or to poly(ADP-ribose) polymerase than toward oligo(ADP-ribose) bound to cytoplasmic proteins from mitochondria or mRNA ribonucleoprotein although the Km and Vmax values were dependent on the chain length (n). In contrast, cytoplasmic glycohydrolase purified from human erythrocytes was more active toward oligo(ADP-ribose) (n = 2.6 or 4.2) bound to the cytoplasmic proteins than to poly(ADP-ribose) (n = 14.6) bound to histone H1, and their kinetic parameters of glycohydrolase II were rather dependent on the acceptor molecules for (ADP-ribose)n. These results suggest that poly(ADP-ribose) glycohydrolase I may play an important role in regulation of poly(ADP-ribosyl)ation levels on chromosomal proteins in nuclei.

Amino Acids↗
PubMed1992

Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase.

Oligomeric ellagitannins (nobotanins B, E, and K) were found to be potent inhibitors of poly(ADP-ribose) glycohydrolase purified from mouse mammary tumor 34I cells. Kinetic analysis revealed that the inhibition of nobotanin B (dimer) was competitive with respect to the substrate poly(ADP-ribose), whereas nobotanin E (trimer) and nobotanin K (tetramer) exhibited mixed-type inhibition. These results suggest that the dimeric structure of ellagitannin may have a functional domain that competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule. To determine the inhibitory effects of oligomeric ellagitannins on poly(ADP-ribose) glycohydrolase in vivo, we examined their effects on de-poly(ADP-ribosyl)ation of some chromosomal proteins in intact 34I cells that was induced by glucocorticoid treatment. Nobotanin B caused concentration-dependent inhibition of glucocorticoid-induced de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in intact 34I cells. Interestingly, this inhibition was associated with suppression of the glucocorticoid-sensitive mouse mammary tumor virus (MMTV) mRNA synthesis. In contrast, nobotanin E and K had little inhibitory effect on either de-poly(ADP-ribosyl)ation of these proteins or induction of MMTV transcription after glucocorticoid treatment. Nobotanin B but not E and K was taken into 34I cells. These results may suggest that the suppression of glucocorticoid-sensitive MMTV transcription results from in vivo inhibition of poly(ADP-ribose) glycohydrolase by nobotanin B. These results also indicate the importance of de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in regulation of transcription of the glucocorticoid-sensitive MMTV gene.

Animals↗
PubMed1992

Purification of a novel B cell growth and differentiation factor associated with lupus syndrome.

We have previously reported that KML1-7 cells cloned from a lupus-prone MRL/l mice produced a soluble factor that preferentially expanded anti-DNA antibody production across the H-2 barrier. We purified this factor, a 55-kDa protein that we termed nucleobindin (Nuc). Nuc showed not only induction of anti-ssDNA IgG antibody in cultures of B cells from MRL/l mice (greater than 16 weeks old), but also growth activity. Furthermore, antibodies against existing cytokines have so far not been shown to block Nuc activity on these B cells. In view of the fact that Nuc did not boost anti-ssDNA IgG antibody production in cultures of spleen cells of comparable age from MRL/n mice, which develop a mild form of lupus after the age of one year, Nuc may act on pre-activated B cells to help IgG anti-DNA antibody production. Taken together, Nuc is a new kind of growth and differentiation factor associated with lupus syndrome.

Animals↗
PubMed1992

Inhibition of human immunodeficiency viral replication by tannins and related compounds.

Among 87 chemically defined tannins and related compounds, several hydrolyzable tannins, but not condensed tannins or other lower molecular weight polyphenols, significantly inhibited both the cytopathic effect of human immunodeficiency virus (HIV) and the expression of HIV antigen in human lymphotropic virus type I (HTLV-1)-positive MT-4 cells. The 50% effective concentrations (2.0-4.8 micrograms/ml) of the active compounds were 13- to 15-fold lower than their 50% cytotoxic concentrations. Their anti-HIV activity was demonstrated to be mediated, at least in part, by inhibition of HIV adsorption to the cells.

Adsorption↗
PubMed1991

Characterization of two forms of poly(ADP-ribose) glycohydrolase in guinea pig liver.

A poly(ADP-ribose) glycohydrolase from guinea pig liver cytoplasm has been purified approximately 45,000-fold to apparent homogeneity. The cytoplasmic poly(ADP-ribose) glycohydrolase designated form II differed in several respects from the nuclear poly(ADP-ribose) glycohydrolase I (Mr = 75,500) previously purified from the same tissue (Tanuma et al., 1986a). The purified glycohydrolase II consists of a single polypeptide with Mr of 59,500 estimated by a sodium dodecyl sulfate-polyacrylamide gel. A native Mr of 57,000 was determined by gel permeation. Peptide analysis of partial proteolytic degradation of glycohydrolases II and I with Staphylococcus aureus V8 protease revealed that the two enzymes were structurally different. Amino acid analysis showed that glycohydrolase II had a relatively low proportion of basic amino acid residues as compared with glycohydrolase I. Glycohydrolase II and I were acidic proteins with isoelectric points of 6.2 and 6.6, respectively. The optimum pH for glycohydrolases II and I were around 7.4 and 7.0, respectively. The Km value for (ADP-ribose)n (average chain length n = 15) and the Vmax for glycohydrolase II were 4.8 microM and 18 mumol of ADP-ribose released from (ADP-ribose)n.min-1.(mg of protein)-1, respectively. The Km was about 2.5 times higher, and Vmax 2 times lower, than those observed with glycohydrolase I. Unlike glycohydrolase I, glycohydrolase II was inhibited by monovalent salts. ADP-ribose and cAMP inhibited glycohydrolase II more strongly than glycohydrolase I. These results suggest that eukaryotic cells contain two distinct forms of poly(ADP-ribose) glycohydrolase exhibiting differences in properties and subcellular localization.

Amino Acids↗
PubMed1991

Mono-ADP-ribosylation of Gs by an eukaryotic arginine-specific ADP-ribosyltransferase stimulates the adenylate cyclase system.

An arginine-specific ADP-ribosyltransferase, named ADP-ribosyltransferase A, was partially purified from human platelets using polyarginine as an ADP-ribose acceptor. When human platelet membranes were incubated with the transferase A in the presence of NAD+, Gs, a stimulatory guanine nucleotide-binding protein of the adenylate cyclase was specifically mono-ADP-ribosylated. ADP-ribose transfer to Gs by this enzyme was suppressed when membranes were pre-ADP-ribosylated by cholera toxin. Incubation of membranes with the transferase A resulted in activation of the adenylate cyclase system. This stimulatory effect of the transferase A on the adenylate cyclase system was inhibited by the presence of polyarginine. These results indicate a role of ADP-ribosyltransferase A in regulation of the adenylate cyclase system via endogenous mono-ADP-ribosylation of Gs.

ADP Ribose Transferases↗