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Biomedical subjects

A Endo

Publications and source records attributed to A Endo.

At least 289 records · Page 16Linked to original sources
PubMed1980

Intracellular localization of two molecular forms of membrane acid protease in Aspergillus oryzae.

The intracellular localization of two forms of membrane-bound acid protease (M1 and M2) [EC 3.4.23.6] of Aspergillus oryzae (Tsujita, Y. & Endo, A. (1978) Eur. J. Biochem. 84, 347-353) was investigated. When the mycelia were treated with wall-lytic enzymes, M2 remained in the cells but most of M2 was solubilized and released. The cell wall fraction obtained by mechanical disruption of the mycelia contained less than 5% of the total acid protease activity in the cells. Subcellular fractionation of the membranes obtained from burst spheroplasts showed that the acid protease was present in both rough and smooth microsomes. Acid protease M1 was predominant in the former and M2 in the latter, possibly on the surface of the cytoplasmic membranes.

Aspergillus↗
PubMed1979

Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals.

ML-263B (compactin), a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, is very effective in lowering serum cholesterol levels in animal species such as hens, dogs, monkeys and man. In the present studies, the effect of this drug on cholesterol metabolism in several strains of mice and rats was studied. The results indicate that, when administered for a longer period, the drug showed no hypocholesterolemic activity in these species under either normo- or hypercholesterolemic conditions, except for rats treated with the detergent Triton WR-1339. The administration of ML-236B caused a significant decrease in fecal excretion of bile acids and in the hepatic levels of cholesterol 7 alpha-hydroxylase, and produced a marked increase in hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase activity, resulting in no inhibition of hepatic sterol synthesis, even in the presence of the drug in the active form(s). It is concluded that the lack of hypocholesterolemic activity of ML-236B in mice and rats could, at least partly, be explained by these unexpected results.

Animals↗
PubMed1979

Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The fungal metabolite ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, has been shown to be significantly effective in lowering serum cholesterol levels in cynomolgus monkeys at doses of 20-50 mg/kg per day. Levels of serum phospholipids and triglycerides were, however, not significantly changed by the administration of the drug. Of the serum lipoprotein fractions, a beta-lipoprotein corresponding to low density lipoprotein was preferentially reduced by the drug treatment. Fecal excretion of neutral sterols was unaffected but that of bile acids and slightly elevated by the administration of ML-236B.

Animals↗
PubMed1979

Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, significantly reduced both serum cholesterol and phospholipid levels in dogs, when used at a dosage higher than 10 mg/kg per day. Triglyceride levels were not consistently changed, but beta- and pre-beta-lipoproteins were preferentially reduced. Serum cholesterol levels were reduced by 44--45% at the higher dosage of 100--400 mg/kg per day (for 5 weeks) but ML-236B caused no significant changes in the cholesterol content of the liver and aorta and in the activities of serum GOT, GPT, CPK and lecithin : cholesterol acyltransferase. Fecal excretion of neutral sterols was unaffected but that of bile acids was markedly elevated by the drug. Under these conditions, hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis, showed no detectable changes.

Animals↗
PubMed1979

Mutagenic effects of cadmium on mammalian oocyte chromosomes.

When female golden hamsters were treated with cadmium chloride at the oogenesis stages of diakinesis/metaphase I to metaphase II, oocytes with the chromosomal complements of hyperhaploidy and diploidy, as well as oocytes at the anaphase-I stage, were observed. Oocytes of this species were especially sensitive to cadmium. Chromosome analysis of metaphase-II oocytes seems to be a useful method for the screening of mutagenicity of environmental contaminants in mammalian germ cells in vivo.

Animals↗
PubMed1978

Purification and characterization of the two molecular forms of membrane acid protease from Aspergillus oryzae.

Two forms (M1 and M2) of the membrane-bound acid protease of Aspergillus oryzae have been purified by extraction with Triton X-100, washing with cold acetone, and repeated gel filtration on Bio-Gel A-15 m in the presence and absence of Triton X-100. The purified membrane enzymes, M1 and M2, moved as a single band in acrylamide gel electrophoresis and had apparent molecular weights of 150 000 and 60 000, respectively, as estimated by sodium dodecyl sulfate/acrylamide gel electrophoresis. These two membrane enzymes activated bovine pancreatic trypsinogen and had the same pH optima in the acid pH range. They immunologically cross-reacted with each other and with an extracellular acid protease from A. oryzae, and contained carbohydrate, ranging from 52.5 to 80.5% and comprising three hexoses, glucose, galactose, and mannose. While these catalytic, chemical and immunological properties are similar to those of the extracellular acid protease from A. oryzae, both membrane enzyme differed in their hydrophobic properties from external enzymes. Thus they are activated by the detergent Triton X-100 and some polar lipids.

Aspergillus↗
PubMed1978

Isolation of 4.5-dihydroxyisophthalic acid an inhibitor of brain glutamate decarboxylase, produced by a Streptomyces species.

A potent inhibitor of brain glutamate decarboxylase (L-glutamate 1-carboxy-lyase, EC 4.1.1.15) was isolated from cultures of a Streptomyces species, and its structure was found to be 4,5-dihydroxyisophthalic acid. The metabolite inhibited beef brain glutamate decarboxylase 50% at a concentration of 0.12 microgram/ml (0.61 micron). The kinetic analysis indicated that 4,5-dihydroxyisophthalic acid was a competitive inhibitor having a Ki value of 0.18 micron.

Animals↗
PubMed1978

Presence and partial characterization of internal acid protease of Aspergillus oryzae.

The presence and partial characterization of the internal acid protease (EC 2.4.23.6) of Aspergillus oryzae has been investigated. Although the majority of the acid protease is external and present in the culture filtrate, a significant amount of the active enzyme is firmly bound to the cells; it is not released by repeated extraction of cells with 0.9% sodium chloride but is liberated into the soluble fraction during disruption of cells. The internal acid protease, as well as the external one, was separated into two major molecular forms (F1 and F2) with molecular weights of 60,000 and 42,000, respectively, by chromatography on Sephadex G-100 and on CM-Sephadex C-50. The partially purified internal enzymes had the same catalytic and immunological properties, as did the external enzyme.

Aspergillus↗
PubMed1978

Specific inhibition of desmosterol synthesis by ML--236B in mouse LM cells grown in suspension in a lipid-free medium.

The suspended growth of LM cells in a lipid-free chemically defined medium was almost completely inhibited in the presence of 0.1 microgram/ml of ML-236B, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate limiting enzyme in cholesterol biosynthesis in mammalian cells. This inhibition was effectively counteracted by adding a small amount of either mevalonate or cholesterol (dispersed in delipidated calf serum) to culture medium. The synthesis of desmosterol, the end product of sterol biosynthesis in LM cells, from [14C]acetate in cultured cells was highly sensitive to ML-236B, being inhibited 35 and 60% at its concentrations of 0.1 and 1 ng/ml, respectively, while the incorporation of [3H]mevalonate into desmosterol was not affected by ML-236B at concentrations up to 0.1 microgram/ml. Synthesis of fatty acids, phospholipids, triglycerides and macromolecules like DNA, RNA and protein were not suppressed by 10 microgram/ml of ML-236B. Desmosterol content of LM cells was reduced by treatment with ML-236B. These results indicate that ML-236B inhibited cell growth via specific interference in the pathway of sterol biosynthesis, presumably on the step catalyzed by HMG-CoA reductase.

Animals↗