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Biomedical subjects

K Saeki

Publications and source records attributed to K Saeki.

At least 145 records · Page 8Linked to original sources

Site-specific mutagenesis of Rhodobacter capsulatus ferredoxin I, FdxN, that functions in nitrogen fixation. Role of extra residues.

One of the two [4Fe-4S]-type clusters of the Rhodobacter capsulatus ferredoxin I, FdxN, was modified through site-specific mutagenesis of the distinctive features of the second cluster-binding motif, Cys38-X2-Cys41-X8-Cys50-X3-Cys54-X4-Cys59. First, various mutagenized products were tested to learn whether they could rescue the decreased capacity of an fdxN-null strain MSA1 to fix nitrogen: the phenotype of MSA1 was reassessed to Nifs (slow growth by nitrogen fixation) from our previous description of Nif- (Saeki, K., Suetsugu, Y., Tokuda, K., Miyatake, Y., Young, D. A., Marrs, B. L. and Matsubara, H. (1991) J. Biol. Chem. 266, 12889-12895). Substitution of Cys59 to Ser yielded an almost fully active product, while that of Cys54 did not. Gradual deletions and deletion-substitution of the 8 residues between Cys41 and Cys50 also yielded active products. Second, three of the modified FdxN proteins were subjected to purification. Only the GA protein, whose 8 residues between positions 42 and 49 were replaced by the Gly-Ala sequence, was purified. The GA protein and the authentic FdxN showed similar optical properties. The two clusters in the former had Em values of -490 and -430 mV, while those in the latter had an identical value of -490 mV, when determined by EPR analysis. It was concluded that: 1) Cys59 is not a ligand to [4Fe-4S] clusters but is important for structural integrity, 2) the residues between positions 42 and 49 may form a "loop-out" from a structure analogous to the Peptococcus aerogenes ferredoxin, and 3) the loop-out region does not have functional significance in nitrogen fixation but may be responsible for maintaining the highly negative redox potential of one of the two clusters.

Amino Acid Sequence↗

Tropomyosin-binding site(s) on the Dictyostelium actin surface as identified by site-directed mutagenesis.

To identify tropomyosin-binding site(s) on the surface of actin molecule, we examined the effect of mutagenesis introduced to subdomain 4 of actin. Because the sequence of Gln228-Ser232 of Dictyostelium actin differs from that of Tetrahymena actin that does not bind tropomyosin, the Dictyostelium/Tetrahymena chimeric actin was produced. Also, Lys238 and Glu241 were replaced with alanine (mutant 645) to study the role of charged residues which are located at both ends of a beta-sheet. As a control experiment, a negative charge was introduced near to the N-terminus (mutant 663). To facilitate the separation of mutant actins without affecting the normal function, Glu360 was replaced with histidine. As a control mutant to such mutants, the mutant 647 (E360H) was produced. Mutant actins were expressed in Dictyostelium cells. All mutant actins were functional: they (i) polymerize and (ii) activate ATPase activity of rabbit skeletal myosin subfragment-1 (S1). The mutant 663 (G2E) showed tropomyosin binding and activated myosin ATPase almost as well as rabbit skeletal actin. However, the tropomyosin binding of the mutant 645 (K238A/E241A/E360H) became magnesium dependent. The chimeric actin (mutant 646: QTAAS-to-KAYKE replacement and E360H) showed decreased tropomyosin binding even in the presence of magnesium ions. These results indicate that the tropomyosin-binding sites of "on"-state actin are on subdomain 4. Surprisingly, the chimeric actin showed more cooperative calcium regulation than rabbit skeletal actin in the presence of tropomyosin-troponin. The mutant actin 645 can hardly activate S1 ATPase irrespective of calcium concentration in the presence of tropomyosin-troponin, even though this actin by itself can activate S1 ATPase. The steric blocking or cooperative/allosteric mechanism of thin filament regulation is discussed.

Actins↗

Presence of macrophage migration inhibitory factor (MIF) in ependyma, astrocytes and neurons in the bovine brain.

We investigated the immunohistochemical localization of a cytokine macrophage migration inhibitory factor (MIF) in the bovine brain. MIF was present in the ependymal cell linings of the cerebral ventricles throughout. Double immunostaining of the section with anti-glial fibrillary acidic protein (GFAP) antibody and with anti-MIF antibody showed that the astrocytes present in subependymal layer were immunoreactive for MIF. In the hippocampus, the pyramidal cells in the CA3 and CA4 subfields and the granule cells of the dentate gyrus were immunoreactive. The bundles of mossy fibers were stained along their projections to CA3 and CA4 regions. The nuclei of the subpopulation of these MIF-immunoreactive cells were also immunostained. These results indicated the widespread distribution of a cytokine, MIF, in the bovine brain and suggested the possibility that MIF might play additional roles than a proinflammatory mediator role in the brain.

Animals↗

Limulus kexin: a new type of Kex2-like endoprotease specifically expressed in hemocytes of the horseshoe crab.

A Kex2-like protease was identified in hemocytes of the horseshoe crab (Tachypleus tridentatus), named limulus kexin, and a full-length cDNA was obtained from a hemocyte cDNA library. The deduced amino acid sequence contains 752 residues, composed of five domains with a signal sequence, a propeptide, a catalytic domain, a Ser/Thr-rich domain, and a transmembrane domain. The domain organization is very similar to that of the yeast Kex2 except that limulus kexin does not have a cytoplasmic tail. The catalytic domain exhibits striking sequence identities with those of furins, especially Drosophila furin1 (79%). Northern blotting showed specific expression of limulus kexin in hemocytes, suggesting the involvement in proteolytic processing of the granule components of hemocytes.

Amino Acid Sequence↗

Identification of a promoter region in the rat prion protein gene.

We have demonstrated the presence of a rat prion protein (RaPrP) gene promoter upstream of multiple initiation sites. A 0.1-kb fragment upstream of the 5'-untranslated region contains specific DNA motifs characteristic of promoter elements including an AP-1 binding site, an inverted CCAAT motif and three inverted Sp-1 binding sites. This fragment directs transcription of a luciferase reporter gene in pheochromocytoma cells (PC12) and rat glioma cells (C6), suggesting that it contains the promoter for the RaPrP gene. To more precisely localize the transcription regulatory elements in this region, a series of 5'-deletion mutants were generated. Deletion analysis showed that an inverted CCAAt and adjoining Sp-1 binding sequences may play an important role in transcription of the RaPrP gene.

Animals↗

The prevalence of Toxoplasma antibody in patients with various ocular diseases in central Japan.

BACKGROUND: Ocular toxoplasmosis has been considered to be a largely asymptomatic infection because of the high seroprevalence of Toxoplasma antibodies and the low rate of clinical diagnosis. On the other hand, Toxoplasma infection has been reported to be associated with the other ocular disease. To investigate the association of Toxoplasma infection with the development of various ocular diseases, we studied Toxoplasma seroprevalence in patients with various ocular diseases. METHODS: We investigated Toxoplasma seroprevalence in 982 patients with various ocular diseases in central Japan. Then we compared the seroprevalence of anti-Toxoplasma antibodies. RESULTS: Of 982 patients with various ocular diseases, 122 (12.4%) had serological evidence of previous exposure to Toxoplasma gondii. There were no statistically significant differences among the patients with various ocular diseases. However, the seroprevalence in patients aged 40 to 99 years with macular degenerative lesions was significantly higher than that in patients without these lesions (P < 0.05, Yates' correction). CONCLUSION: This result suggests that Toxoplasma infection could play some role in the development of a type of macular degenerative lesion.

Adolescent↗

Mercury concentrations in hair from populations in Wau-Bulolo area, Papua New Guinea.

Total mercury (Hg) concentrations were determined in scalp hair from the populations in the Wau-Bulolo area, eastern Papua New Guinea (PNG), where humans are exposed to large quantities of Hg through gold-mining activities by Hg amalgamation processes. Humans living upstream and not engaged in gold mining had a mean hair Hg concentration of 0.55 micro g g-1 (range: 0.19-1.1 micro g g-1 (n = 80), which was recognized as the background level in this area. In contrast, the populations involved in gold-mining activities had a significantly higher level of hair Hg (mean: 1.2 micro g g-1, range: 0.39-3.0 micro g g-1 (n = 86) than the background level, indicating direct or indirect exposure to Hg from gold mining. The hair Hg level in populations downstream of the gold-mining area was significantly higher than the background level, due to the consumption of Hg-contaminated fish. Mercury concentrations were significantly higher in males than in females, regardless of location properties.

Adolescent↗

Three-exon structure of the gene encoding the rat prion protein and its expression in tissues.

The prion protein (PrP), encoded by a chromosomal gene, is associated with development of the neurodegeneration of prion-induced diseases. Since determination of the complete structure of the gene encoding PrP is important for understanding gene expression in the central nervous system (CNS), the nucleotide (nt) sequence of the isolated whole gene encoding rat PrP (raPrP) was determined. The rat PrP gene (raPrP) spans 16 kilobases (kb) of the rat genome and contains three exons of 19-47 base pairs (bp), 98 bp, and 2 kb separated by two introns of 2.2 kb and 11 kb. The first and second exons are noncoding, while the third exon contains a short 5' untranslated region, the entire 762-bp open reading frame (ORF), and a 3' untranslated region. The putative raPrP promoter in the 5' flanking region contains putative Sp1, AP-1, and AP-2 binding sites without a consensus TATA box. This TATA box-deficient feature, coupled with the presence of a high G+C content and Sp1-binding sites in the raPrP promoter, characterizes it as a housekeeping gene. Analysis of the raPrP cDNA 5'-end showed that raPrP mRNA transcription was initiated at multiple sites. Northern blot analysis showed that the levels of raPrP mRNA varied among rat tissues, with the highest levels found in the brain and placenta. This determination of raPrP nt sequences, including the introns and the 5' and 3' flanking regions, may make it possible to elucidate cis-acting elements that regulate the expression of this gene in different tissues and cell lines.

Amino Acid Sequence↗

Improved retrograde axonal transport and subsequent visualization of tetramethylrhodamine (TMR) -dextran amine by means of an acidic injection vehicle and antibodies against TMR.

We studied the ability of various dextran amines (DA) to retrogradely label cortical neurons to the full extent of their dendritic configurations. Corticothalamic neurons were labeled by pressure injection of DA into the ventrobasal thalamic nuclei of the rat brain. Of fluorescein-, Texas Red-, Cascade Blue- and tetramethylrhodamine (TMR)-DAs of MW 3000 and TMR-DA of MW 10,000, neurons were most efficiently labeled with TMR-DA of MW 3000. The use of acidic vehicles (pH 1-3) for dissolving TMR-DA enhanced the retrograde labeling, as compared with that of a neutral vehicle. The retrograde labeling with TMR-DA was more clearly demonstrated by using anti-TMR antibodies; the indirect immunofluorescence method with a rhodamine-conjugated secondary antibody and immunoperoxidase method with a peroxidase anti-peroxidase (PAP) complex revealed that the dendrites of many corticothalamic neurons were filled with TMR-DA. The Golgi-like retrograde labeling of TMR-DA visualized by the PAP immunoperoxidase method was comparable with that of biotinylated DA by the avidin-biotinylated peroxidase complex method. Similar Golgi-like dendritic staining was observed among corticospinal neurons after injection of TMR-DA into the corticospinal tract of the spinal cord. Most apical dendrites of corticospinal neurons extended into layer I, whereas those of corticothalamic neurons ended in layer IV or the deep part of layer III. The TMR-DA injection under acidic conditions and immunostaining with the anti-TMR antibodies are considered to be a useful method to visualize the dendrite configuration of cortical projection neurons.

Animals↗

Metal accumulation in tissues of seabirds from Chaun, northeast Siberia, Russia.

Concentrations of four essential elements (Fe, Mn, Zn, and Cu) and two toxic metals (Cd and Hg) were determined in selected tissues of 11 seabird species collected in Chaun, northeast Siberia. In oldsquaw, arctic tern and herring gull, zinc concentrations were correlated with Cd concentrations. Cadmium concentrations in all the species were highest in kidney and Hg in liver. Cd levels in the liver and kidney of herring gulls were higher than those observed from other breeding areas. Similarly, Hg concentrations were also high in the liver of herring gull. High concentrations of Cd and Hg found in some birds from Chaun might have arisen from exposure on migration.

Journal Article↗

Cloning of a serine proteinase inhibitor from bovine brain: expression in the brain and characterization of its target proteinases.

A cDNA encoding of the serine proteinase inhibitor (serpin), B-43, was cloned from the cDNA library of the bovine brain. It encoded 378 amino acids, and the MW of the protein was estimated to be 42.6 kDa, which is consistent with that of the native B-43 purified from the bovine brain. The homology search revealed that B-43 belongs to the ovalbumin branch of the serpin superfamily. Among them, B-43 was most homologous to human placental thrombin inhibitor (PI-6) and its murine counterpart, with the amino acid identity of 76% and 71%, respectively. Northern blot analysis showed that the size of the transcript was 1.4 kb, and that the expression of B-43 in the bovine brain varied depending on the brain regions, i.e. a lower level of expression was observed in the cerebral cortex and the hippocampus compared to the level of expression that was observed in the medulla oblongata. [35S]-labeled B-43 protein was synthesized in vitro by using a rabbit reticulocyte lysate system, which formed complexes with proteinases such as thrombin, trypsin, alpha-chymotrypsin, and 7S nerve growth factor (NGF), but not with urokinase or plasmin. These results, together with the immunohistochemical localization of B-43 in astrocytes and in some neurons which was observed in the previous study suggest that B-43 may be involved in the regulation of serine proteinases present in the brain or extravasated from the blood.

Animals↗

Specific accumulation of mercury and selenium in seabirds.

Total mercury (T-Hg), methyl mercury (MeHg) and selenium (Se) concentrations were determined to elucidate the relationship between Hg and Se levels in the liver of 10 seabird species. Highest concentrations of T-Hg (mean 267 microg/g dry wt), MeHg (mean 25.5 microg/g dry wt) and Se (mean 113 microg/g dry wt) were in the liver of black-footed albatross (Diomedea nigripes). An equivalent molar ratio of 1:1 between T-Hg and Se was found in the liver of individuals which contain over 100 microg Hg/g. However, such a relationship was unclear in other individuals which had relatively low Hg levels. This suggests that Se plays a role in Hg detoxification for those individuals with high Hg. In seabird tissues, Hg and Se levels should be a most important factor determining the relationship between Hg and Se, and fluctuation of Hg burden through molting and the species-specific demethylation capacity would also influence their relationships.

Journal Article↗

Potent mutagenic potential of 4-methylquinoline: metabolic and mechanistic considerations.

4-Methylquinoline (4-MeQ) showed an extraordinarily potent mutagenicity when compared to quinoline and isomeric methylquinolines. The major metabolite of 4-MeQ was 4-hydroxymethylquinoline, which was not mutagenic under the assay condition employed. Deuteration of the methyl group of 4-MeQ resulted in a decrease in the amount of the hydroxymethyl metabolite and an increase in mutagenicity, indicating that hydroxylation of the substituent methyl group is a detoxication process. A 3-chloro derivative of 4-MeQ was proven to be non-mutagenic. 4-Ethyl-quinoline, as well as 4-hydroxymethylquinoline, was much less mutagenic than 4-MeQ. Taking account of the structure-mutagenicity relationship, a possible mechanism is proposed for the potent mutagenic potential of 4-MeQ.

Animals↗

Affinity purification of macrophage migration inhibitory factor/glycosylation inhibiting factor (MIF/GIF) from bovine brain by using a peptide ligand derived from a novel serpin.

We purified macrophage migration inhibitory factor/glycosylation inhibiting factor (MIF/GIF) from bovine brain by using an affinity column with the C-terminal region peptide of a novel serpin as a ligand. The affinity purified preparation showing a single band on SDS-PAGE contained four peptides on RP-HPLC, which were converged into two peptides time-dependently. Sequence analysis and Western blotting revealed that one was identical to bovine MIF/GIF and the other was an N-terminally modified form of MIF/GIF. These results indicated that there exist at least two forms of MIF/GIF in the bovine brain and that they have an affinity for the C-terminal portion of the serpin.

Amino Acid Sequence↗

Induction of cardiac angiotensinogen mRNA and angiotensin converting enzyme (ACE) activity in isoproterenol-induced heart injury.

Effects of isoproterenol (ISO) on the expression of cardiac angiotensinogen mRNA, angiotensin converting enzyme (ACE) activity, and mechanical functions in spontaneously hypertensive rats were investigated. In the acute phase, defined as within 24 h after the subcutaneous injection of ISO 85 mg/kg, cardiac angiotensinogen mRNA was slightly induced, but ACE activity was not. In the subacute phase, defined as within 8 d after ISO treatment on 2 successive d, both angiotensinogen mRNA expression and ACE activity in the heart were markedly induced. ACE activity in serum was not affected by ISO in either phase. In the subacute phase, ISO reduced body weight and blood pressure, increased ventricular weight and calcium content, and impaired cardiac mechanical function. Oral treatment with imidapril (10 mg/kg/d), an ACE inhibitor, 1 h before each ISO treatment and on the following 6 d, improved ventricular hypertrophy, the elevation of the left ventricular end diastolic pressure, the reduction in contractility, and the prolongation of the time constant. Imidapril significantly suppressed both serum and cardiac ACE activity but did not affect cardiac angiotensinogen mRNA expression in the subacute phase. These results indicate that enhancement of cardiac angiotensinogen mRNA and ACE activity is involved in ISO-induced cardiac dysfunction. Imidapril improved ISO-induced cardiac dysfunction, possibly by suppression of the local ACE activity as well as circulating ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗

Intake ratio of water-insoluble dietary fiber to the water-soluble one in Japanese: an estimation on dietary records and the secular consideration on the national nutrition survey.

Thirty-four foods were analyzed in order to determine the content of water-soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). Using the results with the standard table for 227 foods, the intake ratio of IDF/SDF of an average Japanese was calculated for the period 1946-1990. The ratio was 3.22 in 1990 as calculated on the food intakes shown in the national nutrition survey, and the secular change was not detected since 1946 when the ratio was 3.30. The ratio was also shown to be well preserved between types of households including the age of the head. Using dietary records of 60 healthy city workers (average 42.8 years) for 4 weeks, however, the weekly average ratio for an individual was found to vary in the range of 2.25-5.13 although the total average for 60 individuals was 3.33. Thus, the well preserved IDF/SDF intake ratio for an average Japanese showed, on the contrary, a wide variation of food selection between each person.

Adult↗

Effects of nicotine and exposure to cigarette smoke on suppression of local graft-versus-host reaction induced by immobilization stress in mice.

To study the effects of emotional stress on immunological activities and modification of these effects by nicotine or cigarette smoke, we evaluated the effects of immobilization stress on local graft-versus-host (GVH) reaction, a cell-mediated immune response, and the effects of nicotine and cigarette smoke on them. The effects of immobilization stress on GVH reaction and the effects of nicotine and cigarette smoke on them were evaluated in two experiments: in Experiment 1 by applying the stimulations before and immediately after spleen cell transplantation, and in Experiment 2, by applying stimulations after transplantation. Spleen cells of BALB/C mice were injected into the footpad of CBF1 mice, and GVH reaction was examined after 7 days by weighing the popliteal lymph nodes. Immobilization, nicotine administration and inhalation of cigarette smoke were performed either for 5 days before and immediately after the transplantation (Experiment 1) or for 5 days after transplantation (Experiment 2). The weight of the lymph nodes was markedly increased in the control group, indicating GVH reaction, but the reaction was suppressed by immobilization in both experiments. This suppression of GVH reaction by immobilization was antagonized by nicotine administration and exposure to cigarette smoke in Experiment 1 but not in Experiment 2. These findings suggest that nicotine and cigarette smoke induce recovery of immune response suppressed by immobilization stress, especially by increasing the competence of antigen recognition.

Animals↗