bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of vascular dysfunction and blood lipids of insulin‐resistant rats by a marine oil‐based phytosterol compound
Authors: Russell James C. , Ewart H. Stephen , Kelly Sandra E. , Kralovec Jaroslav , Wright Jeffrey L. C. , Dolphin Peter J. 
Published: November 2006

AbstractThe syndrome that is characterized by obesity, insulin resistance, and hyperlipidemia is increasingly prevalent in all prosperous societies. It is now recognized as a major contributor to cardiovascular disease. Vascular dysfunction in the form of hypercontractility and impaired nitric oxide‐mediated relaxation is a significant component of cardiovascular disease, predisposing to ischemic events. The JCR:LA‐cp strain of rats exhibits all major aspects of the obesity/insulin resistance syndrome, including vascular dysfunction and ischemic lesions of the heart. Dietary lipid intake may have a marked effect on plasma lipid levels and, potentially, on vascular disease. We have investigated the effects of a novel preparation, ONC101 (a phytosterol esterified with fish oil), on plasma lipids and vascular function in the insulin‐resistant JCR:LA‐cp rat. Treatment of obese male rats with ONC101 from 8 to 12 wk of age resulted in no change in plasma lipid concentrations at 0.5 g/kg body weight. At the higher dose of 2.6 g/kg, plasma TG fell 50% (1.26 vs. 2.59 mmol/L, P<0.002) and cholesterol esters were significantly reduced (1.34 vs. 1.61 mmol/l, P<0.002). Food intake and body weights were unaffected by ONC101 treatment. At the low dose of 86 mg/kg, the hypercontractility of aortic rings in response to phenylephrine was normalized and the relaxant response to acetylcholine was significantly improved. The results indicate that ONC101 at high doses has significant hypolipidemic effects and, at very low doses, has beneficial effects on endothelial and vascular smooth muscle cell function.
Evidence that leptin contributes to intestinal cholesterol absorption in obese (ob/ob) mice and wild‐type mice
Authors: Igel M. , Lindenthal B. , Giesa U. , von Bergmann K. 
Published: November 2006

AbstractIn the present study, the effect of leptin on intestinal cholesterol absorption was investigated in C57 BL/6 OlaHsd Lepob/Lepob obese (ob/ob) mice and lean C57 BL/6 (wild‐type) mice. Animals were treated either with or without recombinant leptin for 2 wk. Cholesterol absorption was measured by the constant isotope feeding method and indirectly by the ratio of campesterol to cholesterol in serum. In ob/ob mice, cholesterol absorption was significantly higher compared to wild‐type mice [83.4±2.3% (SD) vs. 77.6±1.5%, P<0.01]. Treatment with leptin significantly reduced cholesterol absorption in both ob/ob and wild‐type mice by 8.5 (P<0.001) and 5.2% (P<0.05), respectively. Serum concentrations of campesterol and the ratio of campesterol to cholesterol in ob/ob mice were significantly higher compared to wild‐type mice (2.2±0.3 mg/dL vs. 1.2±0.3 mg/dL, P<0.001; and 36.8±2.8 μg/mg vs. 28.0±3.3 μg/mg, P<0.001). After treatment of ob/ob mice with leptin, concentrations of campesterol and its ratio to cholesterol were significantly lower (2.2±0.3 mg/dL vs. 1.0±0.2 μg/mg, P<0.001; and 36.8±2.8 μg/mg vs. 13.2±2.2 μg/mg, P<0.001, respectively). In wild‐type mice, the ratio of campesterol to cholesterol in serum was also significantly lower after treatment with leptin (28.0±3.3 μg/mg vs. 22.6±5.0 μg/mg, P<0.05). A significant positive correlation (r=0.701, P<0.01) between cholesterol absorption and the ratio of campesterol to cholesterol, in serum was found. It is concluded that leptin contributes to intestinal cholesterol absorption in ob/ob mice and lean wild‐type mice.
Acute pancreatitis decreases pancreas phospholipid levels and increases susceptibility to lipid peroxidation in rat pancreas
Authors: Ferreira Laura , Pérez‐González Nieves , Llanillo Marcial , Julián Calvo Jose , Sánchez‐Bernal Carmen 
Published: November 2006

AbstractThe objective of this study was to analyze whether acute pancreatitis leads to changes in the lipid composition and susceptibility to lipid peroxidation of pancreatic membranes. Total lipids, cholesterol, phospholipids, FA, and lipid peroxidation were determined in the pancreatic tissue of rats treated with cerulein and of control rats. In pancreatitic rats, significant decreases in membrane total phospholipid contents (P<0.05) and in choline and ethanolamine glyceorphospholipid levels (P<0.05 and P<0.01, respectively), with concomitant significantly higher values of their lysoderivative forms, were found. The cholesterol/phospholipid molar ratio increased by 26%. The unsaturation index of the FA profile decreased significantly (P<0.01) as a consequence of a decrease in the arachidonic acid content. Incubation of membranes with xanthine oxidase/hypoxanthine‐Fe2+/ADP resulted in an increase in the production of TBARS in pancreatitic rats compared to controls. In summary, acute pancreatitis causes changes in the lipid composition of rat pancreatic crude membranes and a greater susceptibility of these membranes to lipid peroxidation.
γ‐Tocopheryl quinone stimulates apoptosis in drug‐sensitive and multidrug‐resistant cancer cells
Authors: Jones Kenneth H. , Liu Jennifer J. , Roehm Jennifer S. , Eckel Jason J. , Eckel Tobin T. , Stickrath Chad R. , Triola Craig A. , Jiang Zongcheng , Bartoli Gianna M. , Cornwell David G. 
Published: November 2006

AbstractChemotherapy‐induced cell death is linked to apoptosis, and there is increasing evidence that multidrug‐resistance in cancer cells may be the result of a decrease in the ability of a cell to initiate apoptosis in response to cytotoxic agents. In previous studies, we synthesized two classes of electrophilic tocopheryl quinones (TQ), nonarylating α‐TQ and arylating γ‐and δ‐TQ, and found that γ‐and δ‐TQ, but not α‐TQ, were highly cytotoxic in human acute lymphoblastic leukemia cells (CEM) and multidrug‐resistant (MDR) CEM/VLB100. We have now extended these studies on tumor biology with CFM, HL60 and MDR HL60/MX2 human promyelocytic leukemia, U937 human monocytic leukemia, and ZR‐75‐1 breast adenocarcinoma cells. γ‐TQ, but not α‐TQ or tocopherols, showed concentration and incubation time‐dependent effects on loss of plasma membrane integrity, diminished viable cell number, and stimulation of apoptosis. Its cytotoxicity exceeded that of doxorubicin in HL60/MX2 cells, which express MRP, an MDR‐associated protein. Apoptosis was confirmed by TEM, TUNEL, and DNA gel electrophoresis. Kinetic studies showed that an induction period was required to initiate an irreversible multiphase process. γ‐TQ released mitochondrial cytochrome c to the cytosol, induced the cleavage of poly(ADP‐ribose)polymerase, and depleted intracellular glutathione. Unlike xenobiotic electrophiles, γ‐TQ is a highly cytotoxic arylating electrophile that stimulates apoptosis in several cancer cell lines including cells that express MDR through both P‐glycoprotein and MRP‐associated proteins. The biological properties of arylating TQ electrophiles are closely associated with cytotoxicity and may contribute to other biological effects of these highly active agents.
Farnesol and geranylgeraniol: Prevention and reversion of lovastatin‐induced effects in NIH3T3 cells
Authors: Ownby Susan E. , Hohl Raymond J. 
Published: November 2006

AbstractMevalonic acid‐derived intermediates in the cholesterol biosynthetic pathway have been recognized as being critical to the isoprenylation of a variety of growth‐regulating proteins, including those of the RAS superfamily. Treatment of cells with lovastatin, a hydroxymethylglutaryl coenyme A (HMG‐CoA) reductase inhibitor, depletes cells of mevalonic acid and thus blocks the isoprenylation of proteins in the RAS superfamily. In NIH3T3 cells pretreated with lovastatin, subsequent addition of farnesol (FOH), but not geranylgeraniol (GGOH), reverses lovastatin's block of RAS isoprenylation. Neither FOH nor GGOH prevents lovastatin‐induced inhibition of RAS isoprenylation when added to cells concurrently with lovastatin. In intact cells, 167 μM FOH and 125 μM GGOH decrease incorporation of [14C]acetate into cholesterol by approximately 50 and 75%, respectively. Results suggest that the radiolabel from either [3H]FOH or [3H]GGOH is incorporated into cholesterol. Co‐treatment of cells with lovastatin or mevalonic acid did not significantly alter [3H]FOH or [3H]GGOH incorporation into cholesterol. Lovastatin induces cell rounding; GGOH, but not FOH, both prevents and reverses lovastatin‐induced cell rounding. These results provide additional evidence for the existence of a novel “isoprenoid shunt” that differentially utilizes FOH and GGOH as metabolic precursors for isoprenoids that have been depleted by lovastatin treatment.
Biosynthesis of arachidonic acid in the oleaginous microalga Parietochloris incisa (Chlorophyceae): Radiolabeling studies
Authors: Bigogno Chiara , Khozin‐Goldberg Inna , Adlerstein Daniel , Cohen Zvi 
Published: November 2006

AbstractThe fresh‐water green alga Parietochloris incisa is the richest plant source of the PUFA arachidonic acid (20∶4n−6, AA). To elucidate the biosynthesis of AA in this alga we labeled cultures of P. incisa with radioactive precursors. Pulse chase labeling with acetate resulted in its incorporation via the de novo biosynthesis pathway of FA. However, labeled acetate was also utilized for the elongation of C16 and C18 PUFA. Labeling with [1‐14C]oleic acid has shown that the first steps of the lipid‐linked FA desaturations utilize cytoplasmic lipids. PC and diacylglyceryltrimethylhomoserine are the major lipids involved as acyl carriers for the Δ12 and Δ6 desaturations of oleic acid, leading sequentially to linoleic and γ‐linolenic acids. The latter is released from its lipid carrier and elongated to 20∶3n−6, which is reincorporated primarily into PF and PC and finally desaturated to AA. Galactolipids, mostly monogalctosyldiacylglycerol (MGDG), serve as substrates for the chloroplastic Δ12 desaturase and, apparently, the ω3 desaturation, common to higher plants and many green algae. The predominant sequence desaturates the 18∶1/16∶0 molecular species of MGDG stepwise to the 18∶3n−3/16∶3n−3 molecular species similar to the prokaryotic pathway of higher plants and green algae.
Detection of the 15‐acetate of prostaglandin E2 methyl ester as a prominent component of the prostaglandins in the gorgonian coral Plexaura homomalla
Authors: Schneider Claus , Manier M. Lisa , Hachey David L. , Brash Alan R. 
Published: November 2006

Abstract15R‐Prostaglandin E2 (PGE2) methyl ester 15‐acetate (1) was isolated from the R‐variety of the Caribbean sea whip coral, Plexaura homomalla collected in the Florida Keys. It was present in coral samples from separate collections in 2–10% of the abundance of the major prostaglandin component, PGA2 methyl ester 15‐acetate. The structure of 1 was assigned based on one‐ and two‐dimensional 1H NMR, HPLC, and LC‐MS analyses. A sample of the S‐variety of P. homomalla was found to contain a similar abundance of the corresponding 15S product, prostaglandin E2 methyl ester 15‐acetate. The significance of PGE acetylation is discussed in relation to the proposed mechanism of PGA synthesis in the coral.
Synthesis of (S)‐α‐amino oleic acid
Authors: Magrioti Victoria , Constantinou‐Kokotou Violetta 
Published: November 2006

AbstractAn efficient synthesis of (S)‐α‐amino oleic acid was developed. The fully protected FA derivative was obtained in four steps starting from methyl (2S)‐2‐[bis(tert‐butoxycar‐bonyl)amino]‐5‐oxopentanoate. These steps are (i) olefination of the starting aldehyde with the appropriate phosphonate anion, (ii) hydrogenation of the double bonds, (iii) controlled reduction of ω‐ethyl ester to an aldehyde in the presence of α‐methyl ester, and (iv) a Wittig reaction of the latter aldehyde with the suitable ylide. Free α‐amino oleic acid was prepared after deprotection of the amino group followed by saponification in a total yield of 24%. N‐tert‐Butoxycarbonyl‐protected amino oleic acid and the corresponding amino alcohol were prepared in high yield. The structures of the products have been established by various spectroscopic techniques.
Cardiac and vascular structure and function are related to lipid peroxidation and metabolism
Authors: Steer Peter , Millgård Jonas , Sarabi Dennis M. , Basu Samar , Vessby Bengt , Kahan Thomas , Edner Magnus , Lind Lars 
Published: November 2006

AbstractThe present study investigated possible relationships between left ventricular mass, intima‐media thickness of the carotid artery (IMT), total arterial compliance, and lipid status in a population sample of 58 apparently healthy subjects aged 20 to 69. By stepwise multiple regression analysis, including age, blood pressure, and smoking, left ventricular mass index, measured by M‐mode echocardiography, increased by 13.0 g/m2 for each 1 standard deviation (SD=0.11 μM, r=0.60, P<0.01) increase in plasma malondialdehyde and 9.50 g/m2 per SD increase in plasma 8‐iso‐prostaglandin F2α in women only (SD=8.88 ng/L, r=0.44, P=0.01). Each 1‐SD (SD=0.27 g/L) increase in apolipoprotein B was associated with a 63 μm increase in IMT (r=0.47, P=0.01) and a 0.27 mL/min/m2/mm Hg (r=−0.60, P<0.01) decrease in stroke index/pulse pressure ratio, reflecting total arterial compliance in women. In men, each 1‐SD increase in the proportion of stearic acid (18∶0) in serum cholesterol esters (SD=0.12 percent units) reduced the transmitral E/A ratio, measured by Doppler echocardiography, reflecting left ventricular diastolic function, by 0.10 units (r=−0.29, P<0.05). Thus, important cardiovascular characteristics, such as left ventricular mass, left ventricular diastolic function, carotid IMT, and total arterial compliance, were independently predicted by indices of lipid metabolism and peroxidation in apparently healthy subjects.
Dietary n−3 FA modulate long and very long chain FA content, rhodopsin content, and rhodopsin phosphorylation in rat rod outer segment after light exposure
Authors: Suh Miyoung , Wierzbicki Antony A. , Clandinin M. Thomas 
Published: November 2006

AbstractA previous study has shown that the long and very long chain FA (VLCFA) content of the rat retina responds to changes in dietary n−6/n−3 ratio of the fat fed (1). The present study tested whether similar changes in these FA are associated with alterations in rhodopsin content and rhodopsin phosphorylation after light treatment. Weanling rats were fed diets containing 20% (w/w, 40% energy) fat with either high (4.8%, w/w) or low (1.2%, w/w) n−3 FA. After 6 wk of feeding, half of the animals in each group were exposed to light for 48 h at 350 lx or were kept in complete darkness. In the rod outer segment, the high n−3 diet treatment increased the level of 20∶5n−3 and 22∶6n−3 and reduced the levels of 20∶4n−6 and 24∶4n−6 in PC, PE, and PS. After the feeding of a high n−3 FA diet, total n−3 pentaenoic VLCFA from C24 to C34 increased in PC, whereas the n−6 tetra‐ and pentaenoic VLCFA decreased. No changes occurred in n−3 hexaenoic VLCFA regardless of the level of 22∶6n−3 in the diet. After light exposure, animals fed a high n−3 FA diet showed reduction in 22∶6n−3 as well as in n−6 and n−3 VLCFA in PC. FFA and TG fractions contained increased levels of both 20∶4n−6 and 22∶6n−3 after light exposure. Dark‐adapted rhodopsin content and rhodopsin phosphorylation in the rod outer segment of rats fed the low n−3 FA diet were higher than in animals fed a high n−3 FA diet. After light exposure, animals fed the low n−3 FA diet lost more rhodopsin compared to animals fed the high n−3 FA diet, resulting in less phosphorylation of rhodopsin. Results indicate that the FA composition, rhodopsin content, and phosphorylation in visual cells is influenced by the dietary n−3 FA fed as well as by light exposure. The results also imply that 22∶6n−3 may not be the precursor for synthesis of hexaenoic VLCFA.
Hypolipidemic action of the soybean isoflavones genistein and genistin in glomerulonephritic rats
Authors: Kojima Takashi , Uesugi Takehiko , Toda Toshiya , Miura Yutaka , Yagasaki Kazumi 
Published: November 2006

AbstractEffects of genistein and its glycoside genistin were studied in nephritic rats with endogenous hyperlipidemia. Male Wistar rats with glomerulonephritis caused by a single intravenous injection of nephrotoxic serum were orally given 5 mg of genistein or 8 mg of genistin/d/100 g body weight for 12 d. These isoflavones suppressed nephritis‐induced severe hypercholesterolemia and hypertriglyceridemia, and their hypolipidemic action was almost identical. Fecal steroid excretion was unchanged by administration of the two isoflavones. Genistein inhibited the incorporation of [1‐14C]acetate into cholesterol and FA in liver slices from nephritic rats when added to an incubation buffer, whereas genistin did not. These results suggest that genistin may be hydrolyzed to genistein and that genistein itself and/or its metabolite(s) may be intracorporal entities suppressing hepatic lipid syntheses. They also suggest that the suppression of hepatic lipid synthesis may be one mechanism of the hypolipidemic action of genistein.
Egg ovomucin attenuates hypercholesterolemia in rats and inhibits cholesterol absorption in Caco‐2 cells
Authors: Nagaoka Satoshi , Masaoka Motoki , Zhang Qing , Hasegawa Mineo , Watanabe Kenji 
Published: November 2006

AbstractThis experiment was designed to evaluate the effect of casein or ovomucin (OV) on the micellar solubility of cholesterol and the taurocholate binding capacity in vitro. We also evaluated the effects of casein or OV on cholesterol metabolism in rats and Caco‐2 cells. OV has a significantly greater bile acid‐binding capacity than that of casein in vitro. Micellar cholesterol solubility in vitro was significantly lower in the presence of OV compared to casein. The cholesterol micelles containing OV significantly suppressed cholesterol uptake by Caco‐2 cells compared to the cholesterol micelles containing casein. Consistent with these in vitro findings, OV‐feeding significantly increased the fecal excretion of bile acids or cholesterol compared with casein‐feeding. Serum total cholesterol was significantly lower in rats fed OV than in those fed casein. The concentrations of total lipids in liver were significantly lower in the OV‐fed group compared with the casein group. These results suggest that the suppression of cholesterol absorption by direct interaction between cholesterol mixed micelles and OV in the jejunal epithelia is part of the mechanism underlying the hypocholesterolemic action of OV. OV may also inhibit the reabsorption of bile acids in the ileum, thus lowering the serum cholesterol level.
Evidence in favor of a facilitated transport system for FA uptake in cultured L6 cells
Authors: Marra Carlos A. , Girón María Dolores , Suáre María Dolores 
Published: November 2006

AbstractIn this manuscript we report a study of the transport of FA in L6 muscle cells. Cultured L6 cells took up labeled FA (C10 to C20) as a linear function of time up to 15 min. Thereafter, the rate of uptake gradually declined although it persisted for at least 12 h after the addition of the substrate. Kinetic parameters (Km, Vm, and ko) were determined from a fitted Michaelis‐Menten‐type equation modified by a term for a saturable (linear) component of the measured total uptake. Vm values were different for some of the FA studied, and Km data showed significant differences between saturated and unsaturated FA. The maximal rate of uptake was observed at pH 7.40 for decanoate, palmitate, and eicosatrienoate. Uptake was significantly influenced when the pH of the incubation medium was changed. Experiments designed to study the influence of FA/albumin molar ratio indicated that Vm was dependent on the total (bound and free) concentration of the FA. A concentrative uptake was demonstrated in short‐term experiments with an apparent plateau of 20 and 40 μM for palmitate and eicosatrienoate, respectively. A competitive inhibition was also observed between palmitate as substrate and the other FA. From our results we can postulate that the uptake of FA in L6 cells is the sum of passive diffusion plus a saturable component and that the rate of uptake is dependent on one (or more) protein structures, although their precise characteristics and functions remain to be elucidated.
Platelet phospholipids are differentially protected against oxidative degradation by plasmalogens
Authors: Leray Claude , Cazenave Jean‐Pierre , Gachet Christian 
Published: November 2006

AbstractThe oxidative degradation of phospholipids in the presence and absence of plasmalogens (plasmenyl phosphatidylethanolamine: PPE) was followed by chemical analysis. Human platelet phospholipids, either intact or after removal of PPE by acid treatment, were oxidized with 28 mM 2,2′‐azobis(2‐amidinopropane di‐HCl in Triton X‐100 micelles (detergent/phospholipid 5∶1, mol/mol). PPE (12% of all phospholipids, mol/mol) disappeared about three times more rapidly than glycerophospholipids, whereas sphingomyelin remained unaltered and the lysophosphatidylethanolamine (lysoPE) generated became progressively more unsaturated. After 60 min oxidation, the FA compositions of PS, PC, and PI were similar in extracts with or without plasmalogens. In contrast, diacyl phosphatidylethanolamine (DPE) became more saturated in the absence of PPE. The rate of phospholipid destruction was always unique to each class, but for all phospholipids slowed down in the presence of PPE. This protective effect increased in the order DPE<PS<PC<PI and did not seem to be simply related to the class unsaturation. α‐Tocopherol had no influence on the time courses of the quantities and compositions of the phospholipids, even at a molar ratio of α‐tocopherol to phospholipids four times higher than in platelet membranes. Thus, PPE protected phospholipids efficiently but differentially against peroxidative attack, whereas the contribution of α‐tocopherol appeared to be negligible even at a concentration four times greater than in platelet membranes.
Lung lipid composition in zinc‐deficient rats
Authors: Gomez N. N. , Ojeda M. S. , Gimenez M. S. 
Published: November 2006

AbstractThere have been a limited number of studies investigating surfactant lipid changes in lung with trace elements. The present investigation was designed to examine the effect of moderate zinc deficiency on the lipid metabolism in rat lung. We also evaluated whether zinc deficiency, which is a wide‐spread problem, could play a role in adult respiratory distress syndrome (ARDS). For that purpose, adult male Wistar rats were fed two diets differing in zinc concentration. The rats were divided into two groups. One group was fed a zinc‐deficient diet containing 3 mg Zn/kg, and the other group received a zincadequate control diet with 30 mg Zn/kg according to AIN 93‐M. After 2 mon of treatment, we observed that in the zinc‐deficient group (i) total lipids, phospholipids, and cholesterol increased whereas TG decreased in whole lung; (ii) phospholipid (PC) concentration increased in lamellar bodies and alveolar macrophages and decreased in extracellular surfactant but did not change in microsomes; (iii) protein concentration decreased in whole lung, extracellular surfactant, lamellar bodies, and macrophages; (iv) the incorporation of [Me‐14C]choline into PC (phospholipids) of lung slices increased; and (v) the activity of CTP/phosphocholine cytidylyltransferase bound to the microsomes increased in the lung. These results suggest that the lipid concentration in the lung (especially the phospholipids) is modified directly or indirectly by a zinc‐deficient diet. In a zincdeficient diet, the lung changes the pattern of PC for an adaptive or recovery stage. Therefore, zinc deficiency implications are important for the design of therapies and public health interventions involving targeted zinc supplementation for high‐risk groups or groups with certain diseases, such as ARDS.