| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Biobehavioral basis of coronary-prone behavior in middle-age men. Part II: Serum cholesterol, the Type A behavior pattern, and hostility as interactive modulators of physiological reactivity Suarez, E. C., R. B. Williams, Jr., et al. (1991), Psychosom Med 53(5): 528-37. Abstract: Prior research suggests that the Type A behavior pattern, Cook and Medley Hostility (Ho) scores, and Total Serum Cholesterol (TSC) are positively associated with physiological changes to behavioral stressors. The objective of the present study was to determine whether TSC interacts with the Type A behavior pattern and hostility to affect cardiovascular and neurohormonal responses to a mental arithmetic task (MATH). For Type A individuals, elevated TSC was associated with larger catecholamine and cortisol responses to MATH. In contrast, for Type B subjects, cholesterol was negatively associated with neurohormonal responses. The interaction between Ho score and TSC predicted a similar pattern of responses whereby, in high hostile men only, TSC was positively associated with MATH-induced changes in catecholamines and heart rate. While the mechanisms responsible for the differences in the lipid-reactivity association as a function of coronary-prone behavior measures remain to be elucidated, this differential association may play a role in the heightened risk of coronary disease among hostile Type A men. |
| Biochemical alterations in guinea pig adrenal cortex following administration of PD 132301-2, an inhibitor of acyl-CoA:cholesterol acyltransferase Wolfgang, G. H., J. R. MacDonald, et al. (1995), Life Sci 56(13): 1089-93. Abstract: To assess whether previously reported ultrastructural alterations of adrenocortical mitochondria induced by the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor PD 132301-2 are accompanied by functional deficits in tissue energy stores, phosphorylated adenine nucleotide levels in guinea pig adrenal cortex were quantitated. Adrenals of male guinea pigs were obtained at 1, 2, 6, or 24 hours after oral administration of 100 mg/kg PD 132301-2 or 0.5% methylcellulose vehicle. In treated animals, ATP levels and ATP/ADP ratios were decreased approximately 50% with concurrent increases in AMP. Calculated energy charge was also decreased; these decreases were maximal by 6 hours. Cholesterol esterification in adrenal cortex was inhibited, resulting in progressive accumulation of free cholesterol up to 3-fold over control by 24 hours, consistent with the ACAT inhibitory activity of the drug. These data suggest that PD 132301-2 distributes to the adrenal cortex where early alterations of tissue bioenergetics occur in a time frame consistent with ultrastructural alterations of mitochondria. |
| Biochemical basis for a cholesterol-lowering activity of 2-2"-(1",3"-dioxolane)-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6- nitro-2H-1-benzopyran (SKP-450), a novel antihypertensive agent Lee, E. Y., D. M. Lim, et al. (1999), Biochem Pharmacol 57(5): 579-82. Abstract: Administration (p.o.) of SKP-450, 2-2"-(1",3"-dioxolane)-2-methyl-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H- 1-benzopyran, a novel antihypertensive agent, to hypercholesterolemic Syrian hamsters led to a significant reduction in plasma lipids in a dose-dependent manner, i.e., a 10.8% to 29% reduction in low-density lipoprotein cholesterol at doses of 0.3 to 10 mg/kg of SKP-450. SKP-450 was found to specifically inhibit the hepatic microsomal lanosterol 14alpha-methyl demethylase (14alpha-DM) in a competitive manner (Ki:2.65 microM). Furthermore, a dose-dependent decrease in the 14alpha-DM activity by SKP-450 parallelled the cholesterol synthetic rate in vitro in both the rat hepatic S10 fractions (supernatants at 10,000 g; IC50:20 microM) and Chinese hamster ovary cells (IC50:23 microM). However, this phenomenon was not seen in AR45 cells, which are deficient in 14alpha-DM, suggesting that 14alpha-DM is the major target for the inhibitory action of SKP-450 in regard to cholesterol biosynthesis. |
| Biochemical characterization of cholesterol-3-sulfate as the sole effector for the phosphorylation of HMG1 by casein kinase I in vitro Okano, M., S. Kano, et al. (2001), Biochem Biophys Res Commun 281(5): 1325-30. Abstract: Phosphorylation of high mobility group protein 1 (HMG1) by casein kinase I (CK-I) and potent effectors (inhibitors and activators) of this phosphorylation were investigated in vitro. We found that (i) CK-I phosphorylates specifically threonine residues on HMG1 when incubated with cholesterol-3-sulfate (CH-3S), but no phosphorylation of HMG1 is detected in the presence of other cholesterol related compounds or their sulfated derivatives; (ii) this phosphorylation is selectively inhibited by heparin, but stimulated significantly by 3',4',7-trihydroxy-isofavone at low doses (0.1-3 microM); and (iii) CH-3S directly induces a drastic conformational change in HMG1. The latter finding provides a mechanism to explain how CH-3S alone can induce the phosphorylation of HMG1 by CK-I in vitro. |
| Biochemical consequences of a mutation that controls the cholesterol dependence of Semliki Forest virus fusion Chatterjee, P. K., M. Vashishtha, et al. (2000), J Virol 74(4): 1623-31. Abstract: The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low-pH-triggered membrane fusion reaction that requires cholesterol and sphingolipid in the target membrane. Cholesterol-depleted insect cells are highly resistant to alphavirus infection and were used to select srf-3, an SFV mutant that is approximately 100-fold less cholesterol dependent for infection due to a single amino acid change in the E1 spike subunit, proline 226 to serine. Sensitive lipid-mixing assays here demonstrated that the in vitro fusion of srf-3 and wild-type (wt) virus with cholesterol-containing liposomes had comparable kinetics, activation energies, and sphingolipid dependence. In contrast, srf-3 fusion with sterol-free liposomes was significantly more efficient than that of wt virus. Thus, the srf-3 mutation does not affect its general fusion properties with purified lipid bilayers but causes a marked and specific reduction in cholesterol dependence. Upon exposure to low pH, the E1 spike subunit undergoes distinct conformational changes, resulting in the exposure of an acid conformation-specific epitope and formation of an E1 homotrimer. These conformational changes were strongly cholesterol and sphingolipid dependent for wt SFV and strikingly less cholesterol dependent for srf-3. Our results thus demonstrate the functional importance of fusogenic E1 conformational changes in the control of SFV cholesterol dependence. |
| Biochemical effects of garlic protein diet and garlic oil on glycosaminoglycan metabolism in cholesterol fed rats Mathew, B. C. and K. T. Augusti (1996), Indian J Exp Biol 34(4): 346-50. Abstract: Garlic protein diet or daily administration of garlic oil to 2% cholesterol fed rats controlled significantly the increases in sulphated glycosaminoglycans in their heart and aorta. However hyaluronic acid level increased. UDPG dehydrogenase decreased and several degrading enzymes increased in the aorta on treatment. The effects of treatment were just the reverse in liver. The high percentage of cysteine in garlic protein and the reactive disulphide group in the oil may be responsible for their beneficial effects. |
| Biochemical studies of inherited diseases related to abnormal cholesterol metabolism. I. High-performance liquid chromatographic analysis of bile alcohol glucuronides in cerebrotendinous xanthomatosis Ohshima, A., T. Kuramoto, et al. (1994), Biol Pharm Bull 17(5): 721-3. Abstract: We developed a rapid and simple quantitative method for measuring bile alcohol glucuronides in serum involving high-performance liquid chromatography without group separation and hydrolysis. The assay of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol 3-glucuronide, the major bile alcohol component in serum from cerebrotendinous xanthomatosis patients, with the present method was useful for the diagnosis of cerebrotendinous xanthomatosis. |
| Biochemical studies of the effect of gossypol consumption on cholesterol and residual glucose in fed and protein-energy deficient rats Achedume, A. C., P. U. Nwoha, et al. (1994), Contraception 50(4): 391-5. Abstract: Some biochemical parameters were investigated on gossypol consumption, and were correlated to the level of cholesterol and residual glucose in rat liver. Two groups of animals were used, one group was fed with normal protein diet and the other set was fed with low protein diet. The results show that gossypol produced no apparent biochemical aberration in the liver of normal protein fed and low protein fed rats. It also had no effect on glucose-6-phosphatase and prostate phosphatase. Gossypol consumption had a significant effect on alcohol dehydrogenase. These results indicate no direct involvement of gossypol in sugar uptake but profound influence on the regulation of cholesterol level in the liver. |
| Biochemistry. An absorbing study of cholesterol Allayee, H., B. A. Laffitte, et al. (2000), Science 290(5497): 1709-11. |
| Biodistribution of 4-(14)Ccholesterol-AmBisome following a single intravenous administration to rats Townsend, R. W., A. Zutshi, et al. (2001), Drug Metab Dispos 29(5): 681-5. Abstract: A biodistribution study of 4-(14)Ccholesterol-AmBisome; a unilamellar liposomal preparation of amphotericin B was conducted to support a radiolabeled human study. The radioactive plasma concentration profile (as measured in microg-Eq/ml of cholesterol) was best fit to a sum of three exponentials that yielded alpha-, beta-, and gamma-half-life estimates of 3.0 +/- 0.3, 11.8 +/- 3.7, and 113.4 +/- 32.4 h, respectively. Clearance and the steady state volume of distribution were 4.9 +/- 0.2 ml/h/kg and 341 ml/kg. Recovery data collected up through 96 h demonstrated mass balance and indicated that although the elimination profile in both urine and feces were incomplete, the dominant route of elimination (<2% in urine versus 33% in feces) was feces, presumably via biliary excretion of intact liposome and/or cholesterol. The liver, spleen, and lungs, organs of the reticuloendothelial system known for their rapid uptake of liposomes, presented with the highest levels of radioactivity. Levels in the kidney were 15% of that found in the liver and lungs. |
| Biodistribution of amphotericin B when delivered through cholesterol hemisuccinate vesicles in normal and A. fumigatus infected mice Saxena, S. and P. C. Ghosh (2000), Pharm Res 17(10): 1236-42. Abstract: PURPOSE: This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmB(DOC)). METHODS: ABCV (12 mg/kg wt) and AmB(DOC) (2 mg/kg wt) were intravenously administered to normal and A. fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. RESULTS: It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmB(DOC) significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmB(DOC) (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmB(DOC) administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. CONCLUSIONS: Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy. |
| Biodynamics of cholesterol and bile acids in the lithiasic hamster Khallou, J., M. Riottot, et al. (1991), Br J Nutr 66(3): 479-92. Abstract: By using the isotopic equilibrium method in the young male Syrian hamster, the rates of cholesterol turnover processes, i.e. dietary cholesterol absorption, cholesterol synthesis, cholesterol excretion in the faeces and urine and cholesterol transformation into bile acids, were determined in the hamster receiving a control (C) or a lithogenic diet (L) for 7 weeks. At the end of this period the gall bladder of all animals in group L contained cholesterol gallstones. The coefficient of dietary cholesterol absorption was reduced by 26%, cholesterol synthesis and cholesterol faecal excretion were twofold higher in group L than in group C. Bile acid content in the small intestine was diminished in group L, but bile acid composition was similar in the two groups. The increase in cholesterogenesis in lithiasic animals essentially took place in the liver. Bile acid biosynthesis did not significantly differ in the two groups, but represented only 35% of total cholesterol input (dietary absorption + internal secretion) in group L v. 52% in group C. Thus, in the lithiasic hamster, hepatic synthesis of cholesterol and bile acids are not coupled. The molar percentage of cholesterol in bile was twofold higher in group L than in group C but those of bile acids and of phospholipids were not modified. In the lithiasic hamster the specific activity of biliary cholesterol was similar to that in plasma and liver. Consequently, biliary cholesterol does not derive directly from cholesterol newly synthesized in the liver but from hepatic cholesterol rapidly exchangeable with plasma cholesterol. |
| Biogenic amine turnover and serum cholesterol in suicide attempt Tripodianakis, J., M. Markianos, et al. (2002), Eur Arch Psychiatry Clin Neurosci 252(1): 38-43. Abstract: The investigation of biological correlates of suicidal behavior is important in searching for possible changes in neuronal systems activity related to that behavior, so that pharmacological interventions may be proposed, especially in high-risk subjects. In a sample of 111 subjects admitted in a general hospital after suicide attempt, we studied the turnover of neurotransmitters by measuring the urinary output of the main metabolites of serotonin, dopamine and noradrenaline (5-HIAA, HVA, MHPG respectively), as well as serum cholesterol, and compared them to those of a group of 62 healthy controls. Venous blood samples and urine samples were collected within 24 hours of admission. Psychiatric diagnosis was made according to DSM-IIIR criteria and assessment of suicide intent with Beck's Suicidal Intent Scale (SIS). Fifty-four (54) subjects received the diagnosis of adjustment disorder, 25 of depression, 16 of schizophrenia and 16 of personality disorder. Fourteen subjects (14) had employed a violent mode of attempt. Urinary MHPG was found significantly higher in all diagnostic groups compared to controls. No difference was found concerning the excretion of HVA and 5-HIAA. Serum total cholesterol was found significantly lower both in violent and non-violent attempters compared to controls after correcting for age. No difference in serum cholesterol or MHPG was found between violent and non-violent attempts. Serum cholesterol and MHPG correlated negatively, while the correlations between cholesterol and 5-HIAA or HVA were not significant. Our results confirm previous reports of lower serum cholesterol in attempted suicide. They are also indicative of an increased noradrenaline turnover in subjects who attempt suicide, at least within 24 hours after the attempt. Whether this activation precedes or follows the attempt because of the specific stress, can not be answered at present. |
| Bioimaging TOF-SIMS: localization of cholesterol in rat kidney sections Nygren, H., P. Malmberg, et al. (2004), FEBS Lett 566(1-3): 291-3. Abstract: Here, we show the localization of a whole organic molecule in biological tissue using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Rat kidneys were sectioned by cryoultramicrotomy and dried at room temperature. The samples were covered with a thin silver layer and analyzed in an imaging TOF-SIMS instrument equipped with a Ga(+)-source. The cholesterol signal showed a high concentration in the nuclear areas of the epithelial cells and a lower concentration over areas representing the basal lamina of renal tubules. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells. |
| Biological variability of cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B Marcovina, S. M., V. P. Gaur, et al. (1994), Clin Chem 40(4): 574-8. Abstract: Biological variability is a major contributor to the inaccuracy of cardiovascular risk assessments based on measurement of lipids, lipoproteins, or apolipoproteins. We obtained estimates of biological variation (CVb) for 20 healthy adults and calculated the percentiles of CVb as an expression of the variability of CVb among individuals for cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apo B, and lipoprotein(a) Lp(a) by four biweekly measurements of these analytes. The CVb for the group was approximately 6-7% for cholesterol, HDL cholesterol, apo A-I, and apo B; approximately 9% for LDL cholesterol; and 28% for triglyceride. However, for each analyte, there was a considerable variation of CVb among individuals. For all analytes except Lp(a), there was no relation between the individual's CVb and the analyte concentration. Lp(a) was inversely related to CVb, and there was a very wide variation in the CVb for Lp(a) among the participants, ranging from 1% to 51%. The number of independent analyses to perform to accurately assess an individual's risk for coronary artery disease should be determined on the basis of the individual CVb for a given analyte rather than the average CVb. |
| Biomedicine. Will the real cholesterol transporter please stand up Klett, E. L. and S. B. Patel (2004), Science 303(5661): 1149-50. |
| Biosynthesis of cholesterol linoleate by polyethylene glycol-modified cholesterol esterase in organic solvents Mori, S., Y. Nakata, et al. (1992), Biotechnol Appl Biochem 15(3): 278-82. Abstract: Cholesterol esterase modified with polyethylene glycol was able to dissolve in some highly hydrophobic solvents such as benzene and toluene, and catalyze the synthesis of cholesterol linoleate with time dependency in the reverse of the usual reaction in aqueous solvents. Enzymatic cholesterol linoleate synthesis followed Michaelis-Menten kinetics which depended on the concentration of cholesterol and linoleic acid. When more than 20 mM of both substrates was used, the specific activity in this esterification was 200-250 nmol/min/mg protein. The apparent Km value for cholesterol and linoleic acid was 3.7 and 7.6 mM, respectively. The possibility of using such a modified enzyme for the synthesis of less stable cholesterol esters is discussed. |
| Biosynthesis of dolichol and cholesterol in rat liver peroxisomes Ericsson, J., E. L. Appelkvist, et al. (1993), Biochimie 75(3-4): 167-73. Abstract: Isolated rat liver peroxisomes contain the complete enzymatic machinery required for the synthesis of both cholesterol and dolichol from farnesyl pyrophosphate. Additionally, the whole or part of the initial portion of the mevalonate pathway between acetyl-CoA and farnesyl pyrophosphate is also present in peroxisomes. Cholesterol and dolichol biosynthesis in peroxisomes is more complete than in ER since peroxisomes contain high concentrations of sterol carrier protein-2, a protein that stimulates both dolichol and cholesterol biosynthesis. Approximately 50 and 20% of the total hepatic dolichol and cholesterol biosynthesis is associated with rat liver peroxisomes, respectively. Upon dietary and drug treatments the synthesis of these lipids displays different regulation in peroxisomes and ER. |
| Biosynthesis of ecdysteroid hormones by crustacean Y-organs: conversion of cholesterol to 7-dehydrocholesterol is suppressed by a steroid 5 alpha-reductase inhibitor Spaziani, E. and W. L. Wang (1993), Mol Cell Endocrinol 95(1-2): 111-4. Abstract: A pair of glands (Y-organs) in crustaceans synthesize and secrete ecdysteroid hormones; the obligate precursor for synthesis is circulating cholesterol. Ecdysteroid output by the Y-organs is regulated negatively by an eyestalk neurosecretory peptide, molt-inhibiting hormone (MIH). The question was addressed, does MIH suppress ecdysteroid synthesis by decreasing cholesterol supply (uptake) or its utilization or both? Experiments were conducted with Y-organs in vitro from the crab, Menippe mercenaria, in the presence of labeled cholesterol, with or without the steroid 5 alpha-reductase inhibitor, L-645390 (Merck). Other experiments superimposed the presence or absence of eyestalk extract containing MIH activity. L-645390 greatly depressed incorporation of cholesterol into an early intermediate, 7-dehydrocholesterol and into secreted ecdysteroids. At the same time, cholesterol accumulated in the Y-organs, to levels significantly higher than in untreated controls. MIH alone depressed both cholesterol uptake and incorporation. MIH together with L-645390 produced the greatest depression of cholesterol incorporation while also preventing the cholesterol accumulation seen with L-645390 alone. These results indicate that cholesterol uptake and its metabolic utilization in Y-organs are separable events representing separate sites of regulation by MIH. |
| Biotinylated theta-toxin derivative as a probe to examine intracellular cholesterol-rich domains in normal and Niemann-Pick type C1 cells Sugii, S., P. C. Reid, et al. (2003), J Lipid Res 44(5): 1033-41. Abstract: BCtheta is a proteolytically nicked and biotinylated derivative of a cholesterol binding protein perfringolysin O (theta-toxin), and has been used to detect cholesterol-rich domains at the plasma membrane (PM). Here we show that by modifying the cell fixation condition, BCtheta can also be used to detect cholesterol-rich domains intracellularly. When cells were processed for PM cholesterol staining, the difference in BCtheta signals between the CT43 (CT) cell, a mutant Chinese hamster ovary cell line lacking the Niemann-Pick type C1 (NPC1) protein, and its parental cell 25RA (RA) was minimal. However, when cells were fixed with 4% paraformaldehyde, they became permeable to BCtheta. Under this condition, BCtheta mainly stained cholesterol-rich domains inside the cells, with the signal being much stronger in CT cells than in RA cells. The sensitivity of BCtheta staining was superior to that of filipin staining. The staining of cholesterol-rich domain(s) inside RA cells was sensitive to beta-cyclodextrin treatment, while most of the staining inside CT cells was relatively resistant to cyclodextrin treatment. Clear differences in intracellular BCtheta staining were also seen between the normal and mutant NPC1 fibroblasts of human or mouse origin. Thus, BCtheta is a powerful tool for visually monitoring cholesterol-rich domains inside normal and NPC cells. |