Eiko Matsumura

Communesins, cytotoxic metabolites of a fungus isolated from a marine alga

Abstract Communesins A and B, exhibiting cytotoxic activity against the cultured P-388 cells, were isolated from the mycelium of a strain of Penicillium sp. stuck on the marine alga Enteromorpha intestinalis . Their structures were elucidated by spectroscopic analyses.

Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta

Chymase shows a catalytic efficiency in the formation of angiotensin (Ang) II. In the present study, the characterization and primary structure of monkey chymase were determined, and the pathophysiological role of chymase was investigated on the atherosclerotic monkey aorta. Monkey chymase was purified from cheek pouch vascular tissue using heparin affinity and gel filtration columns. The enzyme rapidly converted Ang I to Ang II (K m=98 μM, k cat=6203/min) but did not degrade several peptide hormones such as Ang II, substance P, vasoactive intestinal peptide and bradykinin. The primary structure, which was deduced from monkey chymase cDNA, showed a high homology to that of human chymase (98%). The mRNA levels of the aorta chymase were significantly increased in the atherosclerotic aorta of monkeys fed a high‐cholesterol diet. These results indicate that monkey chymase has a highly specific Ang II‐forming activity and may be related to the pathogenesis of atherosclerosis.

Characterization of chymase from human vascular tissues

A chymostatin-sensitive angiotensin II-generating enzyme was found in human gastroepiploic arteries. The enzyme was purified using heparin affinity and gel filtration columns. The molecular mass of the purified enzyme was 30 kDa, and the optimum pH was between 7.5 and 9.0. Enzyme activity was inhibited by soybean trypsin inhibitor, phenylmethylsulfonyl fluoride and chymostatin, but not by ethylenediaminetetraacetic acid, pepstatin and aprotinin. The enzyme rapidly converted angiotensin I to angiotensin II (K(m), 67 mumol/l; Vmax, 43 pmol/s, kcat, 65/s), but did not hydrolyse angiotensin II, substance P, bradykinin, vasoactive intestinal peptide, luteinizing hormone-releasing hormone, somatostatin and alpha-melanocyte-stimulating hormone. The N-terminal sequence was identical to the sequence for human skin/heart chymase. Thus, the chymostatin-sensitive angiotensin II-generating enzyme in human vascular tissues is identified as chymase.

Novel antitumour metabolites produced by a fungal strain from a sea hare

Pericosines A (1) and B (2), and macrosphelides E - H (3 – 6) have been isolated, along with known macrosphelide C (7), from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and their structures have been established on the basis of spectral analyses. Compounds 1 and 2 exhibited significant inhibitory activity in vitro against tumour cells, and the former also showed significant in vivo tumour-inhibitory activity.

Fumiquinazolines, novel metabolites of a fungus isolated from a saltfish

Abstract Fumiquinazolines A, B and C, exhibiting moderate cytotoxicity, were isolated from the mycelium of a strain of Aspergillus fumigatus which existed in the gastrointestinal tract of the saltwater fish Pseudolabrus japonicus . Their structures were elucidated by spectroscopic and X-ray diffraction analyses and chemical evidence.

Halichomycin, a new class of potent cytotoxic macrolide produced by an actinomycete from a marine fish☆

Abstract Halichomycin, produced by a strain of Streptomyces hygroscopicus from the marine fish Halichoeres bleekeri , is a novel class of macrolide with potent cytotoxicity against tumour cells in culture.

A Novel Laccase Inhibitor, N-Hydroxyglycine, Produced by Penicillium citrinum YH-31

A Novel Laccase Inhibitor, N-Hydroxyglycine, Produced by Penicillium citrinum YH-31 Sawao Murao, Yuji Hinode, Eiko Matsumura, Atushi Numata, Kenzo Kawai, Hirofumi Ohishi, Hisanori Jin, Hiroshi Oyama & Takashi Shin a Department of Applied Microbial Technology, The Kumamoto Institute of Technology, Ikeda 4–22–1, Kumamoto 860, Japan b Osaka University of Pharmaceutical Sciences, Matsubara, Osaka 580, Japan Published online: 12 Jun 2014.

Effects of β-Casomorphin-5 on Passive Avoidance Response in Mice

The effects of intracerebroventricular (i.c.v.) injection of bovine β-casomorphin-5 (β-CM-5: Tyr-Pro-Phe-Pro-Gly), a μ-opioid agonist derived from milk β-casein, on step-down type passive avoidance tasks were investigated in mice. Intracerebroventricular administration of a high dose (10 μg) of β-CM-5 produced a significant decrease in step-down latency. β-Funaltrexamine (5 μg, i.c.v.) almost completely reversed the β-CM-5-induced shortening of step-down latency, although neither naltrindole (5 ng, i.c.v.) nor nor-binaltorphimine (5 μg, i.c.v.) had any significant influence on the effect of β-CM-5. Meanwhile, a low dose (0.5 μg, i.c.v.) of β-CM-5 inhibited scopolamine (1 mg/kg)-induced impairment of passive avoidance response. These results indicated that a high dose of β-CM-5 induces amnesia, whereas a low dose ameliorates scopolamine-induced amnesia.

Effects of opioids on neuronal survival in culture of embryonic chick dorsal root ganglion neurons

We studied the effects of endogenous and synthetic opioids on survival of primary-cultured dorsal root ganglion neurons of 8-day chick embryos. In the basal growth medium containing nerve growth factor (NGF), [Leu5]enkephalin, [Met5]enkephalin or selective mu-agonist, [D-Ala2, N-Me-Phe4, Gly5-ol]enkephalin (DAMGO) produced significant increase of neuronal survival in a naloxone-reversible manner. On the other hand, dynorphin A (1-13), [D-Pen2, L-Pen5] enkephalin (DPLPE) (a delta-agonist) and U-50,488 (a kappa-agonist) showed no such effect. No viable neurons were observed in the absence of NGF in spite of the presence of any opioid peptides. These results suggest that [Leu5]enkephalin and [Met5]enkephalin might increase neuronal survival by stimulating mu-opioid receptors, and that these opioid peptides are working with other growth factors but, in and by themselves, do not promote survival.

Prolyl oligopeptidase participates in cell cycle progression in a human neuroblastoma cell line

Prolyl oligopeptidase (POP) is a post-proline cleaving enzyme, which is widely distributed in various organs, with high levels in the brain. In this study, we investigated the effects of a selective POP inhibitor, 3-({4-[2-(E)-styrylphenoxy]butanoyl}-l-4-hydroxyprolyl)-thiazolidine (SUAM-14746), on the growth of NB-1 human neuroblastoma cells. SUAM-14746 treatment for 24-72 h suppresses the growth of NB-1 cells without cell death in a dose-dependent manner (10-60 μM). Similar suppressive effects were observed with another POP inhibitor benzyloxycarbonyl-thioprolyl-thioprolinal. The SUAM-14746-induced growth inhibition in NB-1 cells was associated with pronounced G(0)/G(1) arrest and reduced levels of phosphorylated retinoblastoma protein (pRb), cyclin E, and cyclin dependent kinase (CDK) 2, and increased levels of the CDK inhibitor p27(kip1) and the tumor suppressor p53. SUAM-14746 also induced transient inhibition of S and G(2)/M phase progression, which was correlated with retardation of the decrease in the levels of cyclins A and B. Moreover, RNAi-mediated knockdown of POP also led to inhibition of NB-1 cell growth and the effect was accompanied by G(0)/G(1) arrest. These results indicate that POP is a part of the machinery that controls the cell cycle.