Showing papers by "Akira Endo published in 1993"
TL;DR: While screening for squalene synthetase inhibitors of microbial origin the authors have isolated the same compound from Setosphaeria khartoumensis, and this communication deals with the isolation and mechanism of action of squalestatin 1.
Abstract: synthetase (EC 2.5.1.21) is a microsomal enzyme which catalyzes the two sequential reactions: head-to-head condensation of farnesyl pyrophosphate (FPP) to form presqualene pyrophosphate (PSPP, Fig. 1) and reduction of PSPP to squalene, thus yielding one molecule of squalene from two molecules of FPP4). Recently, several compounds that inhibit squalene synthetase (named squalestatins) have been isolated from Phoma sp. by Dawson et al.5). One of these metabolites, squalestatin 1 (Fig. 1), was demonstrated to be effective in lowering plasma cholesterol in marmosets6). While screening for squalene synthetase inhibitors of microbial origin we have isolated the same compound from Setosphaeria khartoumensis. This communication deals with the isolation and mechanism of action of squelestatin 1. Setosphaeria khartoumensis LI685 was grown aerobically at 25°C for 14 days in a medium containing 2% corn strach, 0.5% glucose, 2.5% soybean meal, 0.5% Farmamedia (Procter & Gamble Oilseed Products Co., U.S.A.), 0.1%
62 citations
TL;DR: The antibiotic patulin was found to inhibit protein prenylation in mouse FM3A cells and reduced incorporation of [3H]mevalonate into proteins by 50% at a concentration of 7 μM.
33 citations
TL;DR: In the course of the search for microbial metabolites which inhibit cholesteryl ester formation in macrophages, helminthosporol, helminethosporal-derived acid, and helminstosporic acid were isolated.
Abstract: acyl-CoA and cholesterol. This enzyme plays key roles in both intestinal absorption of cholesterolX) and cholesteryl ester accumulation in macrophagederived foam cells, which are prominent in atherosclerotic plaques2). In the course of the search for microbial metabolites which inhibit cholesteryl ester formation in macrophages, helminthosporol (1)3), helminthosporal-derived acid (2)4) and helminthosporic acid (3)3) (Fig. 1) were isolated as
15 citations
TL;DR: The antibiotic helvolic acid inhibited cholesteryl ester accumulation in macrophage J774 treated with oxidized low-density lipoprotein (LDL) at a concentration of 50-350 microM, suggesting that this activity accounts for the inhibition of oxidized LDL metabolism in the macrophages.
12 citations
TL;DR: All essential amino acid residues, except 174 and 181, which are implicated in catalysis and binding of NAD and substrates, were conserved among A. nidulans GAPDh and GAPDHs I and II.
11 citations
TL;DR: The effect of BFA was diminished by treatment with low temperature, which is known to abolish BFA effect on Golgi formation, and activity in microsomes from BFA-treated cells was 1.5- to 1.8-fold higher than that from control cells.
7 citations
TL;DR: The time course of the inhibition of cholesterol synthesis by low and high doses of mevinolin and monacolin X were studied in normal human skin fibro Blasts, fibroblasts without low density lipoprotein receptor and HepG2 hepatome cells.
Abstract: The time course of the inhibition of cholesterol synthesis by low and high doses of mevinolin and monacolin X were studied in normal human skin fibroblasts, fibroblasts without low density lipoprotein receptor and HepG2 hepatome cells. Low doses of the inhibitors (0.2 ng/mL) caused a sharp decrease in the rate of cholesterol synthesis during the firt 2–3 h, which gradually increased to about 40% during the next 6 h. Further incubation led to a decrease or stabilization of the cholesterol synthesis rate. High doses of the drugs (100 mg/mL) strongly inhibited cholesterol synthesis during the first 2–3 h, followed by a moderate increase during the next 20 h. No drug or tissue selectivity was observed.
5 citations