bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,3‐oxidosqualene cyclase: From azasqualenes to new site‐directed inhibitors
Authors: Cattel Luigi , Ceruti Maurizio , Balliano Gianni , Viola Franca , Grosa Giorgio , Rocco Flavio , Brusa Paola 
Published: November 2006

Abstract2,3‐Oxidosqualene cyclases (OSC) are enzymes which convert 2,3‐oxidosqualene (OS) into polycyclic triterpenoids such as lanosterol, cycloartenol, and α‐and β‐amyrin. Our interest in the study of OSC is the development of new OSC inhibitors for potential use as hypocholesterolemic, antifungal, or phytotoxic drugs. In particular, we describe the biological activity and the mechanism of a series of acyclic azasqualene derivatives mimicking the C‐2, C‐8, and C‐20 carbonium ions formed during OS cyclization. Some of these carbonium ion analogues are very promising as specific hypocholesterolemic agents. The toxicity, the biodistribution, and the pharmacokinetics of different azasqualene derivatives in mice are also presented. In order to obtain new, site‐directed irreversible inhibitors of OSC, a series of squalene derivatives containing functional groups that can link covalently to an active‐site thiol group was designed. Among these compounds, squalene maleimide was the most active toward mammalian OSC, whereas squalene Ellman behaved as an irreversible inhibitor of OSC from yeast
Growth ofCururbita maxima L. plants in the presence of the cycloartenol synthase inhibitor U18666A1
Authors: Fenner Gregeory P. , Raphiou Ibrahim 
Published: November 2006

AbstractSquash, like other Cucurbitaceae, have unique sterol profiles that offer an excellent opportunity to examine the relationship between sterol biosynthesis and plant growth. To determine the effect of sterol biosynthesis inhibition on squash growth, Cucurbita maxima seedlings with and without cotyledons were subjected to increasing concentrations of the cycloartenol synthase (EC 5.4.99.8) inhibitor 3β‐(2‐diethylaminoethoxy) androstenone (U18666A). Inhibition of shoot growth was concentration‐dependent (from 0, 2, 5, 10, and 20 μM); plants with intact cotyledons grew to 26.4, 23.7, 21.6, 20.0, and 15.6 cm, respectively, at the above inhibitor concentrations, compared to 25.5, 19.4, 17.0, 12.0, and 11 cm for plants with severed cotyledons. In plants with severed cotyledons, 10 and 20 μM U18666A caused rapid necrosis of the first two, newly emerged, primary leaves, and halted new leaf formation. Secondary root formation was initially affected at all inhibitor concentrations regardless of whether cotyledons were present or not. Vegetative tissue showed a decrease in the accumulation of the major squash sterol, 7, 22‐stigmastadienol, accompanied by increased accumulation of minor sterol components. Sterol profiles in cotyledons were unaltered. The data show that sterols are crucial for maintaining plant growth and viability, but do not address the cotyledonary effect on growth with respect to sterol biosynthesis.
Quantitation of steryl ferulate andp‐coumarate esters from corn and rice
Authors: Norton Robert A. 
Published: November 2006

AbstractThe principal steryl ferulate andp‐coumarate esters of different fractions from processed corn brans and corn oils, unrefined and refined, and from rice bran and rice bran oil were quantified by high‐performance liquid chromatography. The results show that hexane‐extracted corn oils yield more than five times the amount of esters compared to expeller processed oils. The yields of esters from bran and related products ranged from 0.07 to 0.54 mg/g of bran. Unrefined corn oils had levels from 0.18 to 8.6 mg/g for oil from hexane‐extracted bran. By comparison, rice bran had ester levels of 3.4 mg/g of bran, and rice bran oil had levels of 15.7 mg/g of oil. The predominant esters from corn were sitostanyl and campestanyl ferulate, and sitostanyl and campestanylp‐coumarate. The principal esters from rice bran were cycloartenyl, 24‐methylenecy‐cloartanyl, and campesteryl ferulate. Rice bran oils had low levels of 24‐methylenecycloartanyl but high levels of cyclobranol esters. The data presented provide a direct comparison of steryl ferulate andp‐coumarate levels in the two cereals, and will aid in selecting the most suitable sources for the isolation of these compounds from corn products.
Mechanism of lysophosphatidylcholine accumulation in the ischemic canine heart
Authors: Mock Thomas , Man Ricky Y. K. 
Published: November 2006

AbstractThe metabolism of lysophosphatidylcholine (LPC) in non‐ischemic and ischemic canine heart was investigated byin vitro enzyme analysis. Selected subcellular fractions were assayed for the LPC‐producing enzyme phospholipase A and the LPC‐eliminating enzymes LPC:acyl‐CoA acyltransferase, LPC:LPC transacylase and lysophospholipase. The canine heart was found to contain all enzymes differing, however, in subcellular distribution and specific activity. Phospholipase A activity did not change significantly in any of the fractions prepared from the ischemic tissue of hearts rendered ischemic for 1, 3 or 5 hr when compared to non‐ischemic tissue. Changes in the activity of the microsomal LPC:acyl‐CoA acyltransferase over the course of 5 hr of ischemia were observed. Significant decreases in the activity of the cytosolic and microsomal lysophospholipases were detected especially after 3 and 5 hr of ischemia. Similarly, a decrease in the activity of the microsomal LPC:LPC transacylase was noted after 3 and 5 hr of ischemia. Our results suggest that impaired catabolism of LPC rather than an enhanced production of LPC is the principal mechanism for the increase in LPC levels in the ischemic canine heart.
Palmitic acid‐labeled lipids selectively incorporated into platelet cytoskeleton during aggregation
Authors: Packham M. A. , Guccione M. A. , Bryant N. L. , Livne A. 
Published: November 2006

AbstractPrevious experiments showed that during the early stages (20–30 seconds) of aggregation induced by adenosine diphosphate (ADP, 2 μM) or thrombin (0.1 U/mL) of rabbit or human platelets prelabeled with [3H]palmitic acid, labeled lipid became associated with the cytoskeleton isolated after lysis with 1% Triton X‐100, 5 mM EGTA [ethylene glycol‐bis‐(β‐aminoethyl ether)]‐N,N,N',N'‐tetra‐acetic acid. The association appeared to be related to the number of sites of contact and was independent of the release of granule contents. We have now investigated the nature of the labeled lipids by thin‐layer and column chromatography and found differences between the distribution of the label in intact platelets (both stimulated and unstimulated) and the isolated cytoskeletons. In both species and with either ADP or thrombin as aggregating agent, 70–85% of the label in both intact platelets and in the cytoskeletons was in phospholipids. The distribution of label among the phospholipids in the cytoskeletons was similar to that in intact platelets except that the percentage of label in phosphatidylcholine was significantly higher in the cytoskeletons of human platelets than in the intact platelets, and the percentage of label in phosphatidylserine/phosphatidylinositol was significantly lower in the cytoskeletons of rabbit platelets and thrombin‐aggregated human platelets than in intact platelets. The cytoskeletons contained a lower percentage of label in triacylglycerol, diacylglycerol, and cholesterol ester than the intact platelets. Contrary to a report in the literature, we found no evidence for the incorporation of diacylglycerol and palmitic acid into the cytoskeleton. Although intact rabbit platelets had more label in ceramide (6.7±2.9%) than intact human platelets (1.5±0.9%), platelets of both species exhibited a three‐ to four‐fold enrichment of labeled ceramide in the cytoskeletons. Thus phospholipids and ceramide that are readily labeled with palmitic acid are selectively incorporated into the cytoskeleton during the initial stages of platelet aggregation.
Effect of excess dietary calcium on colon mucosal membranes and fecal lipids
Authors: Awad Atif B. , Short Mary E. , Fink Carol S. 
Published: November 2006

AbstractThe objective of the present studies was to examine the biochemical alterations in colon apical membranes upon feeding excess calcium to animals on a saturated fatty acid‐rich diet. It has been suggested recently that excess dietary calcium may offer a protection to colon membranes as judged by histologic examination. Sprague‐Dawley weanling male rats were fed a semisynthetic diet containing 14% beef fat plus 2% corn oil and either the calcium requirement or excess calcium in the form of calcium carbonate. Animals were fed the diets for 4 weeks. Feces were collected in the last 3 days. The results indicate that excess dietary calcium resulted in alteration in the density of 4 protein bands of colon apical membranes upon examination on SDS‐gel electrophoresis. These bands contain 20% of membrane proteins. The diet had no effect on either the lipid content or fatty acid composition of the membranes. Excess dietary calcium resulted in 54% reduction in fecal water bile acids and a 44% reduction in fecal water free fatty acids. The reduction in fecal water lipids was due to alterations in the solubility of these lipids. This was not mediated through alterations in the pH of fecal water. The observed alterations in protein patterns of these membranes may be due to either the reduction of fecal water bile acids and free fatty acids or may be a direct effect of dietary calcium on membrane proteins.
Cell separation ofTethya aurantia, an analytical study of embryonic and differentiated sponge cells
Authors: Zimmerman Mary P. , Hoberg Max , Ayanoglu Eser , Djerassi Carl 
Published: November 2006

AbstractThe cells of the spongeTethya aurantia var.californiana were separated on a Ficoll density gradient and the fractions analyzed for cell types and their lipids. Major cell types were choanocyte, archeocyte, and symbiont. Major differences in archeocyte and choanocyte fatty acid composition were noted for 20∶4, 26∶1 and 26∶2. The fatty acids 26∶1, 26∶2, and 28∶3 were dominant in the phosphatidylcholine fraction. Archeocytes had highest concentrations of 4,7,10,13–20∶4 and 5,8,11,14–20∶4 (arachidonic) acids which could be derived from symbionts, as odd‐chain and methyl‐branched fatty acid were also present. Sterol analyses showed cholesterol as a major sterol of the sponge cell fractions and clionasterol (or its 24‐isomer) as a major sterol in symbiont cells.
Structure activity relationships of imidoN‐alkyl semicarbazones, thiosemicarbazones and acethydrazones as hypolipidemic agents in rodents
Authors: Chapman James M. , DeLucy Pierre , Wong Oi T. , Hall Iris H. 
Published: November 2006

AbstractA series of nitrogen substitutedN‐butan‐3‐one derivatives of cyclic imides (phthalimide, substituted phthalimide,o‐benzosulfimide, 1,8‐naphthalimide, 2,3‐dihydrophthalazine‐1,4‐dione and diphenimide) and their semicarbazone, thiosemicarbazone and acethydrazone derivatives were investigated for hypolipidemic activity in rodents. These compounds were generally potent hypolipidemic agents, lowering serum cholesterol levels on an average of 37% and serum triglyceride levels on an average of 29% after 16 days dosing at 20 mg/kg day intraperitoneally (I.P.) in mice. Several analogs, most notably the semicarbazone and acethydrazone derivatives of 1‐N‐(1,8‐naphthalimido)‐butan‐3‐one, demonstrated improved hypocholesterolemic activity relative to their ketone percursors. Similarly, the acethydrazone derivatives generally resulted in improved hypotriglyceridemic activity in each series of 2‐(3‐oxobutyl)‐2,3‐dihydrophthalazone‐1,4‐dione analogs tested. The thiosemicarbazones in mice generally resulted in a loss in hypolipidemic activity. Select compounds, 1‐N‐3‐methylphthalimido butan‐3‐semicarbazone (Ig) and 1‐(4‐methoxyphthalazine‐1(2H)‐one)yl butan‐3(N‐acetyl)hydrazone (IVg), at 10 mg/kg/day orally administered to rats demonstrated potent hypolipidemic activity after 14 days. These compounds lowered liver, small intestine mucosa and aorta wall tissue lipids, e.g. cholesterol and triglycerides, and raised fecal excretion of cholesterol moderately and of triglyceride significantly. Rat serum lipoprotein fractions after treatment for 14 days showed that the two agents lowered VLDL cholesterol and raised HDL cholesterol content.
Separation and detection of phospholipid hydroperoxides in the low nanomolar range by a high performance liquid chromatography/irothiocyanate assay
Authors: Mullertz Anette , Schmedes Anne , Hølmer Gunhild 
Published: November 2006

AbstractA new method for the detection of phospholipid hydroperoxides in the low nanomolar range has been developed by using a high performance liquid chromatography system combined with a post‐column reaction. The detection is based on the oxidation of Fe(II) to Fe(III) by hydroperoxides and the subsequent formation of an ironthiocyanate complex, which can be determined spectrophotometrically at 505 nm. By this method it is possible to separate and quantitate phosphatidylethanolamine hydroperoxide and phosphatidylcholine hydroperoxide formed in erythrocyte ghost membranes during photo‐oxidation.
Hydrolysis of fluorescent pyrene‐acyl esters by human pancreatic carboxylic ester hydrolase and bile salt‐stimulated lipase
Authors: Negre‐Salvayre Anne , Abouakil Nehza , Lombardo Dominique , Salvayre Robert 
Published: November 2006

AbstractFluorescent esters containing pyrenedecanoic acid (P10) or pyrenebutanoic (P4) acid (P4cholesterol, P10cholesterol, P4‐ and P10‐containing triacylglycerols) were synthesized and used as substrates for human pancreatic carboxylic ester hydrolase and bile salt‐stimulated lipase from human milk. Both enzymes were purified by immunoaffinity chromatography. All fluorescent pyrene derivatives were hydrolyzed by pancreatic carboxylic ester hydrolase and bile salt‐stimulated lipase, but at different rates. The hydrolytic rates of the “short” acyl esters (P4‐containing esters) were higher than those of the “long” ones (P10‐containing esters). Conditions were optimized for sensitivity of the assay using fluorescent cholesteryl esters. The pH optimum was 7.5–8.0. Sodium cholate exhibited a stronger activating effect than taurocholate or taurodeoxycholate (maximal activation was achieved with 5 mmol/L cholate and with a molar ratio cholesteryl ester/cholate around 1∶10). Both pancreatic carboxylic ester hydrolase and bile salt‐stimulated lipase from milk were strongly inhibited by the other amphiphiles tested, namely phosphatidylcholine and Triton X‐100, and were inactivated by low concentrations (10 μmol/L) of the serine‐reactive diethyl‐paranitrophenyl phosphate (E600). Both enzymes were strongly inhibited by relatively low concentrations of plasma low density lipoproteins. These studies indicate that the fluorescent esters containing pyrene fatty acids can be used as substrates for assaying and investigating the properties of pancreatic carboxylic ester hydrolase as well as bile salt‐stimulated lipase from milk.
Gas chromatographic analysis of reactive carbonyl compounds formed from lipids upon UV‐irradiation
Authors: Dennis K. J. , Shibamoto T. 
Published: November 2006

AbstractPeroxidation of lipids produces carbonyl compounds; some of these, e.g., malonaldehyde and 4‐hydroxynonenal, are genotoxic because of their reactivity with biological nucleophiles. Analysis of the reactive carbonyl compounds is often difficult. The methylhydrazine method developed for malonaldehyde analysis was applied to simultaneously measure the products formed from linoleic acid, linolenic acid, arachidonic acid, and squalene upon ultraviolet‐irradiation (UV‐irradiation). The photoreaction products, saturated monocarbonyl, α,β‐unsaturated carbonyls, and β‐dicarbonyls, were derivatized with methylhydrazine to give hydrazones, pyrazolines, and pyrazoles, respectively. The derivatives were analyzed by gas chromatography and gas chromatography‐mass spectrometry. Lipid peroxidation products identified included formaldehyde, acetaldehyde, acrolein, malonaldehyde, n‐hexanal, and 4‐hydroxy‐2‐nonenal. Malonaldehyde levels formed upon 4 hr of irradiation were 0.06 μg/mg from squalene, 2.4 μg/mg from linolenic acid, and 5.7 μg/mg from arachidonic acid. Significant levels of acrolein (2.5 μg/mg) and 4‐hydroxy‐2‐nonenal (0.17 μg/mg) were also produced from arachidonic acid upon 4 hr irradiation.
Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs. Minimal requirements of linoleic acid
Authors: Bourre J. M. , Piciotti M. , Dumont O. , Pascal G. , Durand G. 
Published: November 2006

AbstractStarting three weeks before mating, 12 groups of female rats were fed different amounts of linoleic acid (18∶2n−6). Their male pups were killed when 21‐days‐old. Varying the dietary 18∶2n−6 content between 150 and 6200 mg/100 g food intake had the following results. Linoleic acid levels remained very low in brain, myelin, synaptosomes, and retina. In contrast, 18∶2n−6 levels increased in sciatic nerve. In heart, linoleic acid levels were high, but were not related to dietary linoleic acid intake. Levels of 18∶2n−6 were significantly increased in liver, lung, kidney, and testicle and were even higher in muscle and adipose tissue. On the other hand, in heart a constant amount of 18∶2n−6 was found at a low level of dietary 18∶2n−6. Constant levels of arachidonic acid (20∶4n−6) were reached at 150 mg/100 g diet in all nerve structures, and at 300 mg/100g diet in testicle and muscle, at 800 mg/100 g diet in kidney, and at 1200 mg/100 g diet in liver, lung, and heart. Constant adrenic acid (22∶4n−6) levels were obtained at 150, 900, and 1200 mg/100 g diet in myelin, sciatic nerve, and brain, respectively. Minimal levels were difficult to determine. In all fractions examined accumulation of docosapentaenoic acid (22∶5n−6) was the most direct and specific consequence of increasing amounts of dietary 18∶2n−6. Tissue eicosapentaenoic acid (20∶5n−3) and 22∶5n−3 levels were relatively independent of dietary 18∶2n−6 intake, except in lung, liver, and kidney. In several organs (muscle, lung, kidney, liver, heart) as well as in myelin, very low levels of dietary linoleic acid led to an increase in 20∶5n−3. Dietary requirements for 18∶2n−6 varied from 150 to 1200 mg/100 g food intake, depending on the organ and the nature of the tissue fatty acid. Therefore, the minimum dietary requirement is estimated to be about 1200 mg/100 g (i.e., the level that ensures stable and constant amounts of arachidonic acid).
The response to endotoxin in guinea pigs after intravenous black currant seed oil
Authors: Hirschberg Yulia , Shackelford Alan , Mascioli Edward A. , Babayan Vigen K. , Bistrian Bruce R. , Blackburn George L. 
Published: November 2006

AbstractThe influence on the metabolic response to endotoxin of three days of total parenteral nutrition with lipids high in gammalinolenic acid (18∶3ω6, GLA) compared to soy oil (SO) was examined in acute operatively stressed guinea pigs. GLA is the precursor of dihomogammalinolenic acid (DHLA), the substrate for synthesis of “1” series prostaglandins such as PGE1, which have previously been shown to be protective in endotoxin lung injury and traumatic shock. Guinea pigs fed an intravenous diet containing black currant seed oil (BCO) emulsion (20% GLA) or soy oil emulsion (0% GLA) for 2.5 days had their arterial pH, pCO2, pO2, and bicarbonate measured at baseline and hourly during a 7‐hr infusion of endotoxin (lipopolysaccharide (LPS), 2mg/kg) or saline. Plasma lactate and fatty acid profile analyses were performed at the end of the LPS infusion. Increased levels of GLA and DHLA were present in the plasma phospholipid fraction of animals fed the black currant seed oil diet, while soyfed animals had only trace amounts of GLA. In addition, the ratio of DHLA to arachidonate was higher in animals receiving the black currant seed oil total parenteral nutrition (TPN). After 2 hr of LPS infusion, all animals exhibited the typical shock response resulting in metabolic acidosis characterized by a significant (p<0.05) drop in pH from 7.34±.02 (SO) and 7.39±.02 (BCO) at baseline to 7.14±.05 and 7.22±.04 by 7 hr for SO and BCO groups, respectively. Plasma lactate values at the end of the infusion were significantly elevated compared to saline in both groups (p<0.05). Guinea pigs fed GLA showed no improvement over soy‐fed animals, and actually exhibited a more pronounced metabolic acidosis and increased mortality (50% vs 0%) over the 7 hr of LPS infusion. No beneficial effects of a diet high in GLA were observed in the present study.
Uptake, incorporation and metabolism of (3H)triolein in the isolated perfused rabbit heart
Authors: Weis Margaret T. , Palazzo Anthony J. , Williams J. Lynn , Malik Kafait U. 
Published: November 2006

AbstractThe purpose of these experiments was to study the uptake and metabolism of exogenous triglyceride in the isolated perfused rabbit heart. When infused into the rabbit heart, [9,10‐3H(N)]triolein was retained and incorporated into a lipid fraction that had the chromatographic mobility of authentic triolein. Incorporation of labeled triolein was not likely to be the result of a lipoprotein lipase‐mediated lipolysis/resynthesis cycle, since: (i) The distribution of radioactivity following administration of [3H]oleic acid was markedly different from the distribution of radioactivity following the administration of [3H]triolein; (ii) heparin was administered to the rabbits at the time of sacrifice; and (iii) the hearts were perfused with a protein‐free buffer for 20 min prior to the labelling period. When isoproterenol was administered to hearts labelled with [3H]triolein, there was an increased output of total radioactivity, composed of labelled free fatty acids, diacylglycerol and monoacylglycerol. In these same hearts, there was an increased output of glycerol in response to isoproterenol. However, following the administration of bradykinin or angiotensin II, neither the radioactivity nor the glycerol content of the perfusate was changed. These data suggest that [3H]triolein is selectively incorporated into the triglyceride pool of the isolated perfused rabbit heart. Furthermore, this [3H]triolein is available to hormonally‐activated lipolytic enzymes.
Hepoxilins: A review on their enzymatic formation, metabolism and chemical synthesis
Authors: Pace‐Asciak C. R. , Reynaud Denis , Demin Peter M. 
Published: November 2006

AbstractThis article reviews published evidence describing the enzymatic and nonenzymatic formation and the routes of metabolism of the hepoxilins. Also treated are the major approaches used for the chemical synthesis of these compounds and for some of their analogs.