Inhibition of cholesteryl ester transfer protein by fungal metabolites, L681,512.
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Animals↗
Biomedical subjects
N Tabata
Publications and source records attributed to N Tabata.
Ferroverdins, inhibitors of cholesteryl ester transfer protein produced by Streptomyces sp. WK-5344. I. Production, isolation and biological properties.
Streptomyces sp. WK-5344, a soil isolate, was found to produce structurally related inhibitors of cholesteryl ester transfer protein (CETP). New active compounds, designated ferroverdins B and C, were isolated along with known ferroverdin A from the fermentation broth by solvent extraction, ODS column chromatography and silica gel column chromatography. All ferroverdins showed a dose-dependent inhibitory activity against human CETP. The IC50 values were 21, 0.62 and 2.2 microM for ferroverdins A, B and C, respectively, indicating that ferroverdin B is one of the most potent CETP inhibitors of microbial origin.
Bacteria↗
Ferroverdins, inhibitors of cholesteryl ester transfer protein produced by Streptomyces sp. WK-5344. II. Structure elucidation.
The structures of ferroverdins B and C, novel inhibitors of cholesteryl ester transfer protein, were elucidated by spectroscopic studies including various NMR measurements. They are the complex between one Fe2+ and three ligands, that is, two common p-vinylphenyl-3-nitroso-4-hydroxybenzoates and one hydroxy p-vinylphenyl-3-nitroso-4-hydroxybenzoate for ferroverdin B and one carboxylic acid p-vinylphenyl-3-nitroso-4-hydroxybenzoate for ferroverdin C.
Carrier Proteins↗
Structure-specific inhibition of cholesteryl ester transfer protein by azaphilones.
The effect of thirteen different fungal azaphilones, which have a common 6-iso-chromane-like ring, was tested on cholesteryl ester transfer protein (CETP) activity in vitro. Chaetoviridin B showed the most potent inhibitory activity with an IC50 value of < 6.2 microM, followed by sclerotiorin with an IC50 value of 19.4 microM. Rotiorin, chaetoviridin A and rubrorotiorin had moderate inhibitory activity (IC50 ; 30 approximately 40 microM), but others showed very weak or no inhibitory activity. The relationship between the structures and their inhibitory activity indicated that the presence of an electrophilic ketone(s) and/or enone(s) at both C-6 and C-8 positions in the isochromane-like ring is essential for eliciting CETP inhibitory activity. The transfer activity of both CE and TG was inhibited by sclerotiorin to approximately the same extent (IC50: 14.4 and 10.3 microM, respectively). A model of the reaction suggested that sclerotiorin reacts with a primary amine of amino acids such as lysine in the protein to form a covalent bond.
Animals↗
Zelkovamycin, a new cyclic peptide antibiotic from Streptomyces sp. K96-0670. I. Production, isolation and biological properties.
A new antibiotic termed zelkovamycin was isolated from the fermentation broth of Streptomyces sp. K96-0670 by solvent extraction, ODS column chromatography and preparative HPLC. Zelkovamycin showed antibacterial activity against Xanthomonas oryzae, Acholeplasma laidlawii, Pyricularia oryzae and Staphylococcus aureus.
Anti-Bacterial Agents↗
Zelkovamycin, a new cyclic peptide antibiotic from Streptomyces sp. K96-0670. II. Structure elucidation.
The structure of antibiotic zelkovamycin was elucidated as a cyclic peptide comprising glycyl, 2-aminobutanoyl, 2-amino-2-butenoyl, N-methyl glycyl, alanyl, 1,3-thiazoyl, 7-methoxytryptophanyl and 2-methyldehydrothreonyl residues. The sequence of the amino acids was established by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC, 13C-1H HMBC, 15N-1H HMQC and 15N-1H HMBC NMR experiments.
Anti-Bacterial Agents↗
Roselipins, novel fungal metabolites having a highly methylated fatty acid modified with a mannose and an arabinitol.
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Acyltransferases↗
Roselipins, inhibitors of diacylglycerol acyltransferase, produced by Gliocladium roseum KF-1040.
Gliocladium roseum KF-1040, a marine isolate, was found to produce a series of new inhibitors of diacylglycerol acyltransferase (DGAT). Four active compounds, designated roselipins 1A, 1B, 2A and 2B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and preparative HPLC. The highest production of roselipins was observed when cultured in the medium containing natural sea water. Roselipins inhibit DGAT activity with IC50 values of 15 approximately 22 microM in an enzyme assay system using rat liver microsomes.
Acyltransferases↗
Structure elucidation of fungal beauveriolide III, a novel inhibitor of lipid droplet formation in mouse macrophages.
The structure of fungal beauveriolide III, an inhibitor of lipid droplet formation in mouse macrophages, was elucidated to be cyclo-[(3S,4S)-3-hydroxy-4-methyloctanoyl-L-phenylalanyl-L-alanyl- D-allo-isoleucyl] by spectral analyses and chemical degradation.
Animals↗
Structure elucidation of roselipins, inhibitors of diacylglycerol acyltransferase produced by Gliocladium roseum KF-1040.
The structures of roselipins 1A, 1B, 2A and 2B were elucidated by spectroscopic studies including 1H-1H COSY, 13C-1H COSY, 13C-1H HMQC and 13C-1H HMBC NMR experiments, and degradation experiments. They have the common skeleton of 2,4,6,8,10,12,14,16,18-nonamethyl-5,9,13-trihydroxy-2E,6E, 10E-icosenoic acid modified with a D-mannose and a D-arabinitol. Roselipin A and B groups were stereoisomers at the arabinitol moiety, which esterified the fatty acid from the different terminal hydroxy residue. Roselipin 2 group was 6"-O-acetyl roselipin 1 group.
Acyltransferases↗
Structure elucidation of fungal phenochalasins, novel inhibitors of lipid droplet formation in mouse macrophages.
The structures of phenochalasins A and B were elucidated by spectroscopic studies including various NMR measurements. Phenochalasins A and B have the cytochalasan skeleton of the 21,23-dioxa, 17,22-dione moiety containing unique phenyl and O-methyl phenyl residues at the C-10 position, respectively.
Animals↗
Size of lipid microdroplets effects results of hepatic arterial chemotherapy with an anticancer agent in water-in-oil-in-water emulsion to hepatocellular carcinoma.
We have initially prepared a new drug delivery system for hepatocellular carcinoma (HCC). Using sonication and a detergent, iodinated poppy seed oil (IPSO) can be mixed with an aqueous solution of epirubicin to make a water-in-oil emulsion. The water-in-oil emulsion is further passed through a microporous glass membrane and split into saline to make a long-term inseparable water-in-oil-in-water emulsion (W/O/W) that consists of IPSO microdroplets. To investigate the effect of the size of IPSO microdroplets on the efficacy of injection chemotherapy with W/O/W in patients with HCC, 32 HCC patients were randomly assigned and treated with W/O/W of small IPSO microdroplets (30 micrometers in diameter) containing 60 mg of epirubicin (n = 16, group A) or W/O/W of large IPSO microdroplets (70 micrometers) containing the same amounts of epirubicin (n = 16, group B). Effects were assessed by measuring the percentage of decline of the alpha-fetoprotein (AFP) level in a week from the AFP level immediately before the treatment. The decline was significantly larger in group B (50.5 +/- 19.8, mean +/- S.D.) compared with group A (18.9 +/- 33.1; p <.005). The size of IPSO microdroplets injected into the hepatic artery determines the decrease of serum AFP levels of the patients with HCC.
Alanine Transaminase↗
Morphological changes in traumatized skeletal muscle: the appearance of 'opaque fibers' of cervical muscles as evidence of compression of the neck.
Cervical muscles of 15 cases of compression of the neck and the other traumatized skeletal muscles from 54 autopsy cases were examined histologically and immunohistochemically. Round and thick fibers, that is, opaque fibers were observed in the muscles beneath the compression marks on the neck, whereas in areas where no force had been applied, such fibers did not exist. Furthermore, opaque changes appeared around cavities, which formed within severely compressed injured muscle tissue. The pattern of appearance of opaque fibers in the cases of compression of the neck were mainly divided into two types, 'diffuse' pattern and 'focal' pattern. In both blunt and sharp force injuries, the production of opaque fibers were common in the area directly where damage had been inflicted. In stab wounds especially, the appearance of opaque fibers and wavelike fibers, which fanned out and showed a different color from the other areas, was limited to the marginal zone. These results suggest that there is a close relationship between opaque changes and force. Opaque fibers are probably produced by damage to muscles due to extremely applied force. The high incidence of opaque fibers beneath compression marks on the neck should be regarded as a useful indication of strangulation and/or hanging. Furthermore, the distribution and direction of force to the neck might be presumed by the pattern of opaque fibers in cervical muscles, to a certain extent.
Adolescent↗
A twenty-four-hour occlusive exposure to 1% sodium lauryl sulfate induces a unique histopathologic inflammatory response in the xerotic skin of atopic dermatitis patients.
Twenty-four-hour occlusive exposures of 1% aqueous sodium lauryl sulfate (SLS) produced unique functional and histological responses in patients with atopic dermatitis. Disruption of the stratum corneum barrier, measured by transepidermal water loss, was much greater and longer lasting than in normal controls. In contrast to controls the histologic pattern induced reproduced the typical features of the disease with spongiosis, exocytosis of mononuclear cells and a perivenular infiltrate containing eosinophils. The perivascular infiltrate consisted of CD1a+, CD4+ and HLA-DR+ cells, which was much greater and more persistent in atopics. Eosinophilic major basic protein was abundant in atopics but absent in controls. SLS provocation of atopic dermatitis is a striking experimental example of Koebnerization, in which disruption of the stratum corneum barrier as well as cytokine activation of keratinocytes reproduces the clinical diseases.
Adolescent↗
Induction of human osteoclast-like cells by treatment of blood monocytes with anti-fusion regulatory protein-1/CD98 monoclonal antibodies.
We have developed a new and simple system of human osteoclast formation by fusing peripheral blood monocytes with anti-Fusion Regulatory Protein-1 (anti-FRP-1) monoclonal antibody (mAb). When human blood monocytes were cultured in the presence of anti-FRP-1/CD98 mAbs, polykaryocytes began to appear at approximately 15 h and increased in size with time until 3-4 days of incubation with anti-FRP-1 mAb. These fused cells showed positive staining in tartrate-resistant acid phosphatase, possessed numerous calcitonin receptors, and were capable of bone resorption. These results strongly suggest that anti-FRP-1 antibody-induced multinucleated cells are osteoclasts. Furthermore, FRP-1 antigens were detected in osteoclasts isolated from human bone and in the osteoclast-like cells obtained from human giant cell tumors of bone.
Acid Phosphatase↗
Erabulenols, inhibitors of cholesteryl ester transfer protein produced by Penicillium sp. FO-5637. I.Production, isolation and biological properties.
Penicillium sp. FO-5637, a soil isolate, was found to produce a series of inhibitors of cholesteryl ester transfer protein (CETP). Novel active compounds, designated erabulenols A and B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and HPLC. Erabulenols A and B inhibit human CETP activity with IC50 values of 47.7 and 58.2 microM in an in vitro assay system containing 200 microM BSA, respectively.
Anti-Bacterial Agents↗
Erabulenols, inhibitors of cholesteryl ester transfer protein produced by Penicillium sp. FO-5637. II. Structure elucidation of erabulenols A and B.
Structures of erabulenols A and B, novel fungal inhibitors of cholesteryl ester transfer protein were elucidated by spectroscopic studies including various NMR measurements. Erabulenols consist of a phenalenone skeleton and a 1,2,2-trimethyltetrahydrofuran moiety in common. Erabulenol B possesses an additional 2,6-dihydroxy-5-methyl-3-methylketonyl benzyl moiety. The absolute stereochemistry at the C-2' position of erabulenol A was deduced as S by comparison of the optical rotation with that of other related compounds.
Carrier Proteins↗
Immunohistochemical demonstration of bleeding in decomposed bodies by using anti-glycophorin A monoclonal antibody.
The usefulness of glycophorin A (GPA) as a marker of bleeding was investigated in decomposed bodies by using anti-human GPA monoclonal antibody immunohistochemically. Ninety-one specimens consisting of 37 skin and 54 muscle specimens were obtained from 21 autopsy cases with various degree of decomposition, which ranged from 12 h up to 2-3 months after death. The presence or absence of the bleeding in the specimens was evaluated macroscopically and was divided as follows: (1) specimens without bleeding (31 specimens), (2) specimens with bleeding (15 specimens), and (3) suspect specimens (45 specimens), in which the bleeding was not clear. By a peroxidase-labeled streptavidin-biotin method, positive reaction products for GPA were observed only within the blood vessels in the specimens without bleeding. On the other hand, in the specimens with bleeding, positive reaction products for GPA were seen not only within the blood vessels but also the extravascular tissues. Therefore, a specimen can be diagnosed as bleeding when GPA is distributed both within blood vessels and tissue outside the vessels. In application of GPA to 45 suspect specimens, 42 specimens (93%) were distinguished from the specimens with bleeding or without bleeding. These results prove that GPA is very useful as a marker of bleeding. The detection of GPA by the immunohistochemical method will help to differentiate between bleeding and hemoglobin (Hb) diffusion from blood vessels in a decomposed body.
Adult↗