bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxicity of tocopherols and their quinones in drug‐sensitive and multidrug‐resistant leukemia cells
Authors: Cornwell David G. , Jones Kenneth H. , Jiang Zongcheng , Lantry Laura E. , Southwell‐Keely Peter , Kohar Indrajati , Thornton Donald E. 
Published: November 2006

AbstractCytotoxicities of tocopherols (α‐T, γ‐T, δ‐T), their para (α‐TQ, γ‐TQ, δ‐TQ)‐and ortho (Tocored)‐quinone oxidation products, the synthetic quinone analog of γ‐TQ containing a methyl group substituted for the phytyl side‐chain (TMCQ) and the synthetic quinone analog of Tocored containing a methyl group substituted for the phytyl side‐chain (PR) were measured in acute lymphoblastic leukemia cell lines that are drug‐sensitive (CEM) and multidrug‐resistant (CEM/VLB100). Among tocopherols, only δ‐T exhibited cytotoxicity. Among para quinones, α‐TQ showed no cytotoxicity, while γ‐TQ and δ‐TQ were highly cytotoxic in both CEM and CEM/VLB100 cell lines (LD50<10 μM). δ‐TQ and γ‐TQ were more cytotoxic than the widely studied chemotherapeutic agent doxorubicin, which also showed selective cytotoxicity to CEM cells. The orthoquinone Tocored was less cytotoxic than doxorubicin in drug‐sensitive cells but more cytotoxic than doxorubicin in multidrug‐resistant cells. Cytotoxicity was not a function of the phytyl side‐chain since both TMCQ and PR were cytotoxic in leukemia cells. Cytotoxic para and ortho quinones were electrophiles that formed adducts with nucleophilic thiol groups in glutathione and 2‐mercaptoethanol. Cytotoxicity was enhanced when the glutathione pool was depleted by preincubation with buthionine‐[S,R]‐sulfoximine, but cytotoxicity was diminished by the addition of N‐acetylcysteine to cultures. α‐T also diminished the cytotoxicity of para‐ and or‐thoquinones. Buthionine‐[S,R]‐sulfoximine did not block the inhibitory effect of either N‐acetylcysteine or α‐T, showing that these agents did not act solely by maintaining the glutathione pool as an essential antioxidant system. In conclusion, tocopherylquinones represent a new class of alkylating electrophilic quinones that function as highly cytotoxic agents and escape multidrug resistance in acute lymphoblastic leukemia cell lines.
Conversion of palmitate to unsaturated fatty acids differs in a Neurospora crassa mutant with impaired fatty acid synthase activity
Authors: Stafford Allan E. , McKeon Thomas A. , Goodrich‐Tanrikulu Marta 
Published: November 2006

AbstractThe Neurospora crassa cel (fatty acid chain elongation) mutant has impaired fatty acid synthase activity. The cel mutant requires exogenous 16:0 for growth and converts 16:0 to other fatty acids. In contrast to wild‐type N. crassa, which converted only 42% of the exogenous [7,7,8,8‐2H4]16:0 that was incorporated into cell lipids to unsaturated fatty acids, cel converted 72%. In addition, cel contains higher levels of 18:3δ9,12,15 than wild‐type, and synthesizes two fatty acids, 20:2δ11,14 and 20:3δ11,14,17, found at only trace levels in wild‐type. Thus, the Δ15‐desaturase activity and elongation activity on 18‐carbon polyunsaturated fatty acids are higher for cel than wild‐type. This altered metabolism of exogenous 16:0 may be directly due to impaired flux through the endogenous fatty acid biosynthetic pathway, or may result from altered regulation of the synthesis of unsaturated fatty acids in the mutant.
Identification of ceramide‐phosphorylethanolamine in Oomycete plant pathogens: Pythium ultimum, phytophthora infestans, and Phytophthora capsici
Authors: Moreau Robert A. , Young David H. , Danis Paul O. , Powell Michael J. , Quinn Chad J. , Beshah Kebede , Slawecki Richard A. , Dilliplane Robert L. 
Published: November 2006

AbstractCellular lipids were extracted from three species of Oomycete plant pathogens (Pythium ultimum, Phytophthora infestans, and Ph. capsici) and analyzed via normal‐phase high‐performance liquid chromatography with flame‐ionization detection. The most abundant polar lipids in each of the three species were the polar membrane lipids, phosphatidylethanolamine (PE), phosphatidylcholine, and a phosphosphingolipid that eluted soon after PE. Structural analysis via mass spectrometry and nuclear magnetic resonance spectrometry revealed that the phosphosphingolipid was ceramide phosphorylethanolamine (Cer‐PE). The most abundant molecular species of Cer‐PE in P. ultimum had a molecular weight of 670.5, contained an unusual 19‐carbon branched triunsaturated sphingoid (C19‐Δ4, 8, 10, 9‐methyl long‐chain base) and palmitic acid as the amidelinked fatty acid. The most abundant molecular species of Cer‐PE in Ph. infestans has a molecular weight of 714.5, contained a common 16‐carbon 1,3 di‐OH sphingoid, and erucic (cis 13‐docosenoic, C22‐Δ13) acid as the amide‐linked fatty acid. The Cer‐PE in Ph. capsici comprised a mixture of each of the two molecular species found in P. ultimum and Ph. infestans.
Lipids of Thermococcus hydrothermalis, an archaea isolated from a deep‐sea hydrothermal vent
Authors: Lattuati Agnès , Guezennec Jean , Metzger Pierre , Largeau Claude 
Published: November 2006

AbstractThe membrane lipids of a deep‐sea hydrothermal vent archaea, Thermococcus hydrothermalis, were isolated, purified, and structurally characterized. On the basis of acid methanolysis and spectroscopic studies, the polar lipids, amounting to 4.5% (w/w) of the dry cells, comprised diphytanyl glycerol diethers and dibiphytanyldiglycerol tetraethers, in a 45∶55 ratio. No cyclopentane ring was present in the tetraethers. From the neutral lipids, accounting for 0.4% (w/w) of the dry cells, besides low amounts of di‐ and tetraethers occurring in a free form, four acyclic tetraterpenoid hydrocarbons, di‐ and triunsaturated were identified. All were structurally related to lycopane. The presence of these hydrocarbons provides some evidence that lycopane, widely distributed in oceans, could be derived, at least partially, from the hydrocarbons synthesized by some thermophilic Archaea. Finally, analysis of the uninoculated culture medium indicates that fatty acid derivatives and some steroid and triterpenoid compounds identified in the lipidic extract of the archaea originated from the culture medium.
Fatty acid composition of the cellular slime mold Polysphondylium pallidum
Authors: Saito Tamao , Ochiai Hiroshi 
Published: November 2006

AbstractThe cellular slime mold Polysphondylium pallidum was grown upon Escherichia coli B/r, and the fatty acid compositions of total lipids obtained from vegetative amebae and aggregation‐competent cells were compared. Fatty acids isolated from vegetative cells included C‐17 and C‐19 cyclopropane fatty acids and also straight‐chain, saturated fatty acids. The cyclopropane fatty acids were derived from the ingested bacteria. Development of amebae to aggregation‐competent cells was accompanied by a substantial decrease in saturated cyclopropane fatty acids and a concomitant increase in unsaturated fatty acids and unsaturated cyclopropane fatty acids, mostly as 18∶3 (5,9,12). We report here the fatty acid composition and identify the occurrence of Δ5 desaturation of cyclopropane fatty acids, namely, 9,10‐methylene 5‐hexadecenoic acid and 11,12‐methylene 5‐octadecenoic acid. These fatty acids have not been reported previously in the related species Dictyostelium discoideum, which also feeds on E. coli B/r and has Δ5‐desaturation activity.
Isolation and structure of a new galactolipid from oat seeds
Authors: Hamberg Mats , Liepinsh Edvards , Otting Gottfried , Griffiths William 
Published: November 2006

AbstractSeeds of oat (Avena sativa L.) were recently shown to contain significant quantities of a new hydroxy acid, (15R)‐hydroxy‐(9Z)‐(12Z)‐octadecadienoic acid (trivial name, avenoleic acid). In the present work, avenoleate was found to be mainly (63%) localized in the glycolipid fraction of oat seed lipids. Fractionation of the glycolipids by thin‐layer chromatography and reversed‐phase high‐performance liquid chromatography revealed the presence of a main molecular species which accounted for 20% of the total avenoleate content of oat seeds. Structural studies by chemical methods and mass spectrometry demonstrated that the avenoleate‐containing glycolipid was a galactolipid assembled of one molecule of avenoleic acid, two molecules of linoleic acid, two molecules of D‐galactose, and one molecule of glycerol. Degradation of the new galactolipid by chemical and enzymatic methods demonstrated the localization of acyl chains, i.e., linoleate at sn‐1 and linoleoylavenoleate at sn‐2. Nuclear magnetic resonance spectroscopy gave independent support for this structure and also demonstrated that the two galactoses formed an α‐d‐galactopyranosyl‐1‐6‐β‐d‐galactopyranosyl moiety which was bound to the sn‐3 position. Based on these experiments, the new galactolipid could be formulated as 1‐[(9′Z),(12′Z)‐octadecadienoyl]‐2‐[(15″R)‐{9″′Z), (12″′Z)‐octadecadienoyloxy}‐(9″Z),(12″Z)‐octadecadienoyl]‐3‐(α‐d‐galactopyranosyl‐1‐6‐β‐d‐galactopyranosyl)‐glycerol. Quantitatively, the amount of the avenoleate‐containing galactolipid was of the same order of magnitude as those of individual molecular species of digalactosyldiacylglycerol containing nonoxygenated acyl chains. The content of the new galactolipid in oat seeds was 0.5–0.6 mg per g of seed.
Stoichiometric and kinetic studies on Ginkgo biloba extract and related antioxidants
Authors: Shi Honglian , Niki Etsuo 
Published: November 2006

AbstractOwing to increasing evidence showing the importance of lipid peroxidation in oxidative stress in vivo, the role and evaluation of antioxidants have received much attention. Ginkgo biloba extract (GBE), well‐known as an efficient drug against diseases induced by free radicals, has been suggested to exert its effect by antioxidant action. A method was established to determine the activity of GBE as a hydrogen donor by stoichiometric and kinetic studies, and GBE was compared with several other antioxidants such as α‐tocopherol, propyl gallate, and two kinds of flavonoids which are found in GBE, quercetin, and kaempferol. It was found that there were 6.62×1019 active hydrogens in 1g of GBE. Stoichiometric studies showed that one molecule of α‐tocopherol reacted with one molecule of galvinoxyl radical. For quercetin, kaempferol and propyl gallate, the experimental stoichiometric numbers were 4.0, 1.9, and 3.1, respectively. The rates of reaction of antioxidants with galvinoxyl in ethanol were determined spectrophotometrically, using a stopped‐flow technique. The second‐order rate constant, k2, obtained at 25°C was 0.13 (g/l)−1s−1 for GBE and 5.9×103, 2.1×103, 1.2×104, and 2.4×103 M−1s−1 for quercetin, kaempferol, propyl gallate, and α‐tocopherol, respectively. The second‐order rate constant, k2′, on the molar basis of active hydroxyl groups in the tested substances obtained at 25°C decreased in the order of propyl gallate > α‐tocopherol> quercetin>GBF∼kaempferol. This is the first study on GBE as an antioxidant which reports both stoichiometric and kinetic results.
Lipid molecular order in liver mitochondrial outer membranes, and sensitivity of carnitine palmitoyltransferase I to malonyl‐CoA
Authors: Zammit Victor A. , Corstorphine Clark G. , Kolodziej Marys P. , Fraser Fiona 
Published: November 2006

AbstractMitochondrial outer membranes were prepared from livers of rats that were in the normal fed state, starved for 48 h, or made diabetic by injection of streptozotocin. Membranes were also prepared from starved late‐pregnant rats. The latter three conditions have previously been shown to induce varying degrees of desensitization of mitochondrial overt carnitine palmitoyltransferase (CPT I) to malonyl‐CoA inhibition. We measured the fluorescence polarization anisotropy of two probes, 1,6‐diphenyl‐1,3,5‐hexatriene (DPH) and 1‐(4‐trimethylammoniumphenyl)‐6‐phenyl‐1,3,5‐hexatriene‐p‐toluenesulfonate (TMA‐DPH) which, when incorporated into membranes, report on the hydrophobic core and on the peripheral regions of the bilayer, respectively. The corresponding polarization indices (rDPH and rTMA‐DPH) were calculated. In membranes of all three conditions characterized by CPT I desensitization to malonyl‐CoA, rDPH was decreased, whereas there was no change in rTMA‐DPH, indicating that CPT I is sensitive to changes in membrane core, rather than peripheral, lipid order. The major lipid components of the membranes were analyzed. Although significant changes with physiological state were observed, there was no consistent pattern of changes in gross lipid composition accompanying the changes to membrane fluidity and CPT I sensitivity to malonyl‐CoA. We conclude that CPT I kinetic characteristics are sensitive to changes in lipid composition that are localized to specific membrane microdomains.
Biochemical and structural characterization of triacylglycerol lipase from Penicillium cyclopium
Authors: Ibrik Aida , Chahinian Henri , Rugani Nathalie , Sarda Louis , Comeau Louis‐Claude 
Published: November 2006

AbstractAn extracellular lipase, active on water‐insoluble triacylglycerols, has been isolated from Penicillium cyclopium. The purified enzyme has a molecular mass of 29 kDa by gel filtration and SDS‐polyacrylamide gel electrophoresis. It hydrolyzes emulsions of tributyrin, trioctanoin, and olive oil at the same rate as pancreatic lipase and shows very low activity against partial acylglycerols (monooctanoin and dioctanoin) and methyl esters. It is stable at 35°C for 60 min and has maximal activity in a pH range of 8–10. Hydrolysis of triacylglycerols by P. cyclopium lipase is inhibited by detergents such as Triton X‐100. Comparison of the sequence of the 20 first amino acid residues of P. cyclopium triacylglycerol lipase with other Penicillium lipases indicates a high homology with previously characterized lipases produced by P. expansum and P. solitum which are enzymes of comparable size and substrate specificity. Conversely, homology between P. cyclopium lipase and P. simplicissimum lipase, a nonspecific lipolytic enzyme, is low. Penicillium cyclopium triacylglycerol lipase shows no homology with P. camembertii lipase which is specific to monoacylglycerol and diacylglycerol.
Enhanced macrophage uptake of lipoprotein(a) after Ca2+‐induced aggregate‐formation
Authors: Tanaka Seiya , Yashiro Akira , Tasaki Hiromi , Nakashima Yasuhide 
Published: November 2006

AbstractWe tested the hypothesis that aggregated lipoprotein(a) [Lp(a)] is avidly taken up by macrophages. Lp(a) was isolated by sequential centrifugations and gel chromatography from a patient with high plasma levels of Lp(a) who was being treated with low density lipoprotein (LDL)‐apheresis. Aggregated Lp(a) was prepared by mixing native Lp(a) with 2.5 mmol/L CaCl2, and 54% of the 125I‐Lp(a) aggregated after interacting with CaCl2. The binding and degradation of aggregated Lp(a) in macrophages were 4.6‐ and 4.7‐fold higher than those of native Lp(a), respectively. An excess amount of LDL did not inhibit either increase. Cholesterol esterification in macrophages was markedly stimulated by aggregated Lp(a), and macrophages were transformed into foam cells. Cytochalasin B, a phagocytosis inhibitor, strongly inhibited the degradation and cholesterol esterification (78 and 83%, respectively). These findings suggested that aggregation may be partially involved in Lp(a) accumulation, thereby contributing to the acceleration of atherosclerosis.
Conjugated linoleic acids alter bone fatty acid composition and reduce ex vivo prostaglandin E2 biosynthesis in rats fed n‐6 or n‐3 fatty acids
Authors: Li Yong , Watkins Bruce A. 
Published: November 2006

AbstractThis study evaluated the effects of conjugated linoleic acids (CLA) on tissue fatty acid composition and ex vivo prostaglandin E2 (PGE2) production in rats given diets varying in n‐6 and n‐3 fatty acids. Four groups of rats were given a basal semipurified diet (AIN‐93G) containing 70 g/kg of added fat for 42 d. The fat treatments were formulated to contain CLA (0 vs. 10 g/kg of diet) and n‐6 (soybean oil having an n‐6/n‐3 ratio of 7.3) and n‐3 fatty acids (menhaden oil+safflower oil having an n‐6/n‐3 ratio of 1.8) in different ratios in a 2×2 factorial design. Fatty acids in liver, serum, muscle, heart, brain, spleen, and bone (cortical, marrow, and periosteum) were analyzed by capillary gas‐liquid chromatography. The various dietary lipid treatments did not affect growth; however, CLA improved feed efficiency. The CLA isomers were found in all rat tissues analyzed although their concentrations varied. Dietary CLA decreased the concentrations of 16∶1n−7, 18∶1, total monounsaturates and n−6 fatty acids, but increased the concentrations of n−3 fatty acids (22∶5n−3 and 22∶6n−3), and saturates in the tissues analyzed. Ex vivo PGE2 production in bone organ culture was decreased by n−3 fatty acids and CLA. We speculate that CLA reduced the concentration of 18∶1 fatty acids by inhibiting liver Δ9‐desaturase activity. The fact that CLA lowered ex vivo PGE2 production in bone organ culture suggests that these conjugated fatty acids have the potential to influence bone formation and resorption.
Cycloserine‐induced decrease of cerebroside in myelin
Authors: Miller Sheldon L. , Denisova Lyudmila 
Published: November 2006

Abstractl‐Cycloserine has been shown specifically to lower brain cerebroside levels in vivo, but the extent to which the decrease in whole brain cerebroside content reflects lower myelin cerebroside levels is not known since a substantial portion of cerebroside is found in nonmyelin membranes. The present report demonstrates that chronically administered cycloserine lowers the proportion of cerebroside in rat brain myelin. Cycloserine‐induced decrease of myelin cerebroside should provide a useful tool in investigating the role of cerebroside in maintaining myelin stability.
A 13C nuclear magnetic resonance study of free fatty acid incorporation in acylated lipids in differentiating predipocytes
Authors: Guo Wen , Kirkland James L. , Corkey Barbara , Hamilton James A. 
Published: November 2006

AbstractTo understand the role of free fatty acid (FFA) incorporation in the accumulation of lipids in the adipocyte and ultimately in the development of obesity, 13C nuclear magnetic resonance was used to study lipid metabolism in differentiating preadipocytes. The incorporation of 13C=O‐labeled FFA into cellular lipids in primary cultured rat preadipocytes and 3T3L1 preadipocytes at different stages of differentiation was monitored by the 13C carbonyl chemical shift. Significant incorporation of palmitic acid into phosphatidylcholine in both the α and β acyl chain positions was found in cells at early stages of differentiation. At later differentiation stages or after extended incubation periods, most of the 13C=O signals were found in the triacylglycerol (TG) molecules. Unsaturated 13C=O‐labeled acyl chains were detected in the TG molecules when cells were incubated with saturated 13C=O‐labeled FFA, indicating that intracellular dehydrogenation had occurred in the 13C=O‐labeled palmitoyl chain. By using 13C‐labeled methyl myrisfate as an internal intensity reference, incorporation of 13C FFA into each acyl chain position of the major intracellular lipids was determined quantitatively.
Tocotrienols inhibit the growth of human breast cancer cells irrespective of estrogen receptor status
Authors: Nesaretnam Kalanithi , Stephen Ruth , Dils Ray , Darbre Philippa 
Published: November 2006

AbstractPotential antiproliferative effects of tocotrienols, the major vitamin E component in palm oil, were investigated on the growth of both estrogen‐responsive (ER+) MCF7 human breast cancer cells and estrogen‐unresponsive (ER‐) MDA‐MD‐231 human breast cancer cells, and effects were compared with those of α‐tocopherol (αT). The tocotrienol‐rich fraction (TRF) of palm oil inhibited growth of MCF7 cells in both the presence and absence of estradiol with a nonlinear dose‐response but such that complete suppression of growth was achieved at 8 μg/mL. MDA‐MB‐231 cells were also inhibited by TRF but with a linear dose‐response such that 20 μg/mL TRF was needed for complete growth suppression. Separation of the TRF into individual tocotrienols revealed that all fractions could inhibit growth of both ER+ and ER‐ cells and of ER+ cells in both the presence and absence of estradiol. However, the γ‐ and δ‐fractions were the most inhibitory. Complete inhibition of MCF7 cell growth was achieved at 6 μg/mL of γ‐tocotrienol/δ‐tocotrienol (γT3/δT3) in the absence of estradiol and 10μm/mL of δT3in the presence of estradiol, whereas complete suppression of MDA‐MB‐231 cell growth was not achieved even at concentrations of 10μg/mL of δT3. By contrast to these inhibitory effects of tocotrienols, αT had no inhibitory effect on MCF7 cell growth in either the presence or the absence of estradiol, nor on MDA‐MB‐231 cell growth. These results confirm studies using other sublines of human breast cancer cells and demonstrate that tocotrienols can exert direct inhibitory effects on the growth of breast cancer cells. In searching for the mechanism of inhibition, studies of the effects of TRF on estrogen‐regulated pS2 gene expression in MCF7 cells showed that tocotrienols do not actviaan estrogen receptor‐mediated pathway and must therefore act differently from estrogen antagonists. Furthermore, tocotrienols did not increase levels of growth‐inhibitory insulin‐like growth factor binding proteins (IGFBP) in MCF7 cells, implying also a different mechanism from that proposed for retinoic acid inhibition of estrogen‐responsive breast cancer cell growth. Inhibition of the growth of breast cancer cells by tocotrienols could have important clinical implications not only because tocotrienols are able to inhibit the growth of both ER+ and ER‐ phenotypes but also because ER+ cells could be growth‐inhibited in the presence as well as in the absence of estradiol. Future clinical applications of TRF could come from potential growth suppression of ER+ breast cancer cells otherwise resistant to growth inhibition by antiestrogens and retinoic acid.