| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Investigations of cholesterol transformation during sewage treatment: relevance to estrogen formation pathways? Niven, S. J., J. Snape, et al. (2001), Sci Total Environ 279(1-3): 75-86. Abstract: There is currently a great deal of concern over the observation of so-called estrogenic effects (specifically increases in the concentrations of the egg yolk precursor, vitellogenin) in male fish living in some UK rivers. The effects have been attributed to chemicals, including estrogenic steroids, which enter the rivers via sewage effluents. The origins of these estrogenic steroids in sewage may include contributions from the influents and possibly in situ transformation processes of other steroids occurring during sewage treatment. The present study examined the latter possibility. The bacterial metabolism of radiolabelled cholesterol during laboratory-simulated aerobic sewage treatment was studied by reverse phase radio-high performance liquid chromatography (rHPLC) and radio-gas chromatography (rGC) to examine the hypothesis that cholesterol could undergo A-ring aromatisation to form first, 19-norcholest-1,3,5(10)-trien-3-ol (NCT) and hence, by known bacterial pathways, the estrogenic steroid, estrone. The results showed that, to the contrary, much of the cholesterol (approx. 50% in 96 h) underwent rapid mineralisation to carbon dioxide, consistent with A-ring rupture (rather than aromatisation) and beta-oxidation of the alkyl side chain as major transformation routes. Some polar (early-eluting) rHPLC products were observed, possibly steroidal conjugates and/or fatty acids. Among the minor metabolites detected by rGC and GC-mass spectrometry (GC-MS) were cholest-3,5-diene and a second cholestadiene isomer. However, since alkenes were unexpected in this rHPLC fraction, they may arise as artefacts from thermal decomposition of cholesteryl esters, indicating that some cholesterol esterification had also occurred. In the alcohol rHPLC fractions, cholestadienol was identified by GC and GC-MS but neither NCT or estrone were detected. This suggests that, at least under these simulated conditions, in situ aromatisation of cholesterol to NCT and formation of estrone from NCT were not major processes. |
| Invited commentary: low blood cholesterol, nonillness mortality, and other nonatherosclerotic disease mortality: a search for causes and confounders Jacobs, D. R., Jr., M. F. Muldoon, et al. (1995), Am J Epidemiol 141(6): 518-22. |
| Invited commentary: low cholesterol and nonartherosclerotic disease risk: a persistently perplexing question Jacobs, D. R., Jr. and C. Iribarren (2000), Am J Epidemiol 151(8): 748-51. Abstract: In contrast to clinical trials using statin drugs, which suggest that cholesterol lowering from high to moderate levels is safe, many, but not all, prospective studies report higher nonatherosclerotic disease rates in people with low serum total cholesterol, even after deleting deaths in the 5 years after cholesterol determination. A perplexing and unanswered question is whether low cholesterol is causally related to nonatherosclerotic disease risk. Cholesterol is reduced during the acute phase reaction; a state of immune activation that persists for more than 5 years may explain the prospective observations. Higher cholesterol may be a marker for other protective substances such as fat-soluble antioxidants. Low cholesterol might mark poor nutrition, for example, during depression. Alternatively, higher cholesterol levels may result in enhanced delivery of lipids to cells during the immune response or tissue repair or may enhance defense against endotoxins and viruses. Although we believe that populationwide efforts to lower cholesterol should continue, we think that important biology may be reflected in the repeatedly observed associations of low cholesterol with nonatherosclerotic disease. The authors urge that research continue to elucidate any biologic bases of these relations. |
| Involvement of a cellular surface factor(s) in lipid-free apolipoprotein-mediated cellular cholesterol efflux Li, Q., H. Czarnecka, et al. (1995), Biochim Biophys Acta 1259(3): 227-34. Abstract: Involvement of cellular surface factors in cellular lipid efflux mediated by lipid-free apolipoprotein has been investigated. Lipid-free human apolipoprotein (apo) A-I generated net efflux of cholesterol and phospholipid from mouse peritoneal macrophages and rat aorta smooth muscle cells. Ratio of cholesterol to phospholipid was much lower in the lipid released by this mechanism from the smooth muscle cells than that from the macrophages, in agreement with our previous observation (Li, Q., Komaba, A. and Yokoyama, S. (1993) Biochemistry 32, 4597-4603). On the other hand, free apoA-I did not cause any lipid efflux from human erythrocytes. In contrast, apparent efflux of cellular cholesterol to HDL was similarly observed from all of these three cellular membranes. Trypsin treatment of the cultured macrophages completely inhibited apoA-I-mediated efflux of cholesterol and phospholipid. Smooth muscle cells also showed complete inhibition of the apoA-I-mediated cellular lipid efflux by trypsin treatment except that it required longer incubation with the enzyme. The same cellular treatment with trypsin even by prolonged incubation had only a limited effect on apparent cellular cholesterol efflux to HDL and apolipoprotein-free lipid microemulsions. Thus, free apolipoprotein-mediated cellular lipid efflux seems to depend on a trypsin-susceptible cellular surface factor(s) that erythrocytes may lack, being distinct from physicochemical cholesterol exchange reaction between cell and lipoprotein. |
| Involvement of caveolin-1 in cholesterol enrichment of high density lipoprotein during its assembly by apolipoprotein and THP-1 cells Arakawa, R., S. Abe-Dohmae, et al. (2000), J Lipid Res 41(12): 1952-62. Abstract: High density lipoprotein (HDL) is assembled by interaction of apolipoprotein A-I with human monocytic leukemia cell line THP-1 by removing cellular cholesterol and phospholipid. Although the HDL formed with undifferentiated THP-1 cells contained only phosphatidylcholine and almost no cholesterol, the cells differentiated with phorbol 12-myristate 13-acetate (PMA) generated HDL enriched in cholesterol. The extent of cholesterol enrichment related to the cellular cholesterol level in the differentiated cells, but only weakly in the undifferentiated cells. In contrast, the differentiation had no influence on the diffusion-mediated cellular cholesterol efflux. The undifferentiated cells expressed the messages of ATP-binding cassette transporter 1 and caveolin-1, at low levels, and the PMA-induced differentiation resulted in substantial expression of both messages. Caveolin-1 protein expression was also highly induced by the PMA treatment of THP-1 cells. When the cells were treated with the antisense DNA of caveolin-1 and differentiated, both caveolin-1 synthesis and cholesterol incorporation into the HDL were reduced in parallel to generate the cholesterol-poor HDL.We concluded that caveolin-1 is involved in enrichment with cholesterol of the HDL generated by the apolipoprotein-cell interaction. This function is independent of the assembly of HDL particles with cellular phospholipid and of nonspecific, diffusion-mediated efflux of cellular cholesterol. |
| Involvement of Cdc42 signaling in apoA-I-induced cholesterol efflux Nofer, J. R., R. Feuerborn, et al. (2003), J Biol Chem 278(52): 53055-62. Abstract: Cholesterol efflux, an important mechanism by which high density lipoproteins (HDL) protect against atherosclerosis, is initiated by docking of apolipoprotein A-I (apoA-I), a major HDL protein, to specific binding sites followed by activation of ATP-binding cassette transporter A1 (ABCA1) and translocation of cholesterol from intracellular compartments to the exofacial monolayer of the plasma membrane where it is accessible to HDL. In this report, we investigated potential signal transduction pathways that may link apoA-I binding to cholesterol translocation to the plasma membrane and cholesterol efflux. By using pull-down assays we found that apoA-I substantially increased the amount of activated Cdc42, Rac1, and Rho in human fibroblasts. Moreover, apoA-I induced actin polymerization, which is known to be controlled by Rho family G proteins. Inhibition of Cdc42 and Rac1 with Clostridium difficile toxin B inhibited apoA-I-induced cholesterol efflux, whereas inhibition of Rho with Clostridium botulinum C3-exoenzyme exerted opposite effects. Adenoviral expression of a Cdc42(T17N) dominant negative mutant substantially reduced apoA-I-induced cholesterol efflux, whereas dominant negative Rac1(T17N) had no effect. We further found that two downstream effectors of Cdc42/Rac1 signaling, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), are activated by apoA-I. Pharmacological inhibition of JNK but not p38 MAPK decreased apoA-I-induced cholesterol efflux, whereas anisomycin and hydrogen peroxide, two direct JNK activators, could partially substitute for apoA-I in its ability to induce cholesterol efflux. These results for the first time demonstrate activation of Rho family G proteins and stress kinases by apoA-I and implicate the involvement of Cdc42 and JNK in the apoA-I-induced cholesterol efflux. |
| Involvement of cholesterol in osteoclast-like cell formation via cellular fusion Sato, T., I. Morita, et al. (1998), Bone 23(2): 135-40. Abstract: Osteoclasts, the bone resorbing cells, are formed from hematopoietic precursors via plasma membrane fusion. To investigate the possibility that cholesterol is involved in cellular fusion events, we examined the effects of the depletion of low density lipoproteins (LDL) and the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on osteoclast-like cell formation. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), osteoclast-like cells, were formed as a result of the coculture of mouse spleen cells with mouse stromal cells TMS-14 in the presence of 1alpha, 25-dihydroxyvitamin D3 (1, 25 VD3). The depletion of LDL suppressed the formation of TRAP-positive MNCs, but the effect was abrogated by the addition of LDL. This inhibitory effect was not observed following the depletion of LDL in the early stages of the culture (day 0-3). The decrease in the number of TRAP-positive MNCs resulting from LDL depletion was accompanied by an increase in the number of TRAP-positive mononuclear cells. Furthermore, the formation of MNCs was also suppressed by the addition of simvastatin, an HMG-CoA reductase inhibitor. The inhibitory effect of simvastatin on the generation of TRAP-positive MNCs was dose and time dependent. However, treatment with simvastatin did not affect the increase in TRAP activities. These results suggest that cholesterol in the membranes of monocytes is involved in osteoclast-like cell formation via cellular membrane fusion events. |
| Involvement of cholesterol in the inhibitory effect of dimethyl-beta-cyclodextrin on P-glycoprotein and MRP2 function in Caco-2 cells Yunomae, K., H. Arima, et al. (2003), FEBS Lett 536(1-3): 225-31. Abstract: We compared the inhibitory effect of various cyclodextrins (CyDs) on P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) function and examined the contribution of cholesterol to the inhibitory effect of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CyD) on the efflux activity of the function in Caco-2 cell monolayers. Of various CyDs, DM-beta-CyD significantly impaired the efflux activity of P-gp and MRP2. DM-beta-CyD released P-gp and MRP2 from the monolayers in the apical side's transport buffer and decreased the extent of cholesterol as well as P-gp and MRP2 in caveolae of Caco-2 cell monolayers, but not caveolin and flotillin-1. On the other hand, DM-beta-CyD did not change MDR1 and MRP2 mRNA levels. Therefore, these results suggest that the inhibitory effect of DM-beta-CyD on P-gp and MRP2 function, at least in part, could be attributed to the release of these transporters from the apical membranes into the medium as secondary effects through cholesterol-depletion in caveolae after treatment of Caco-2 cell monolayers with DM-beta-CyD. |
| Involvement of cholesterol-rich lipid rafts in interleukin-6-induced neuroendocrine differentiation of LNCaP prostate cancer cells Kim, J., R. M. Adam, et al. (2004), Endocrinology 145(2): 613-9. Abstract: IL-6 is an inflammatory cytokine that has been linked to aggressive prostate cancer (PCa). Previous studies have demonstrated that IL-6 can enhance the differentiation of PCa cells toward a neuroendocrine (NE) phenotype, a possible indicator of hormone-refractory disease. In this report, we present evidence that the mechanism of IL-6-stimulated NE differentiation employs a detergent-resistant (lipid raft) membrane compartment for signal transduction in LNCaP PCa cells. Signal transducer and activator of transcription (STAT)3, a mediator of IL-6 signaling, was rapidly phosphorylated and translocated to the nucleus in LNCaP cells treated with IL-6. Both processes were inhibited by filipin, a cholesterol-binding compound that disrupts plasma membrane lipid rafts. Isolation of Triton X-100-insoluble raft fractions from LNCaP cells by discontinuous sucrose gradient centrifugation demonstrated that the 80-kDa IL-6 receptor localized almost exclusively to the raft compartment. Although STAT3 was located predominantly in the Triton X-100-soluble subcellular fraction in exponentially growing cells, abundant phosphorylated STAT3 was detected in the raft fraction after stimulation with IL-6. Increases in expression of the NE marker, neuron-specific enolase, and neuron-specific enolase promoter activity after IL-6 treatment were reduced after membrane rafts were disrupted by filipin treatment. LNCaP cells expressed the raft-resident proteins flotillin-2 and G(ialpha2), but notably not caveolins, the predominant structural protein present in caveolar membrane rafts in many tissues and tumor cells. These results are the first to define a role for lipid raft membrane microdomains in signal transduction mechanisms capable of promoting the NE phenotype in PCa cells, and they demonstrate that the raft compartment is capable of mediating such signals in the absence of caveolins. Our results also suggest a mechanistic role for membrane cholesterol in cell signaling events relevant to PCa progression. |
| Involvement of enhanced coagulation and fibrinolysis system in induction of atherosclerosis in hyperlipidemic rabbits fed on a high cholesterol diet Ichino, K., M. Okazaki, et al. (1997), In Vivo 11(2): 115-23. Abstract: We studied the involvement of coagulation and fibrinolysis system in the induction and development of atherosclerosis in rabbits with hyperlipidemia induced by a high-cholesterol diet (HCD). In HCD rabbits, plasma lipids and atherogenic indices were maintained at a high level throughout the experimental period compared with those in rabbits fed on a standard diet. In the early phase, a significant increase in fibrinogen level was followed by increases in the activities of plasminogen and tissue-type plasminogen activator with a decrease in alpha 2-plasmin inhibitor activity and platelet count. In the middle and late phases, significant increases in plasminogen activator inhibitor-1 and antithrombin-III were observed in HCD rabbits. These results suggest that the early enhancement of coagulation followed by high activity of fibrinolysis is involved in the induction and development of hyperlipidemic thromboembolism and atherosclerosis in HCD rabbits. |
| Involvement of high density lipoprotein as substrate cholesterol for steroidogenesis by bovine adrenal fasciculo-reticularis cells Yaguchi, H., K. Tsutsumi, et al. (1998), Life Sci 62(16): 1387-95. Abstract: Adrenocorticosteroids are known to be synthesized from cholesterol which may arise from de novo synthesis or from the uptake of low-density lipoproteins (LDL) or high-density lipoproteins (HDL). LDL is reported to be a main substrate for corticosteroid synthesis by bovine adrenocortical cells, although the role of HDL, which is well known to be used for steroid biosynthesis in rat adrenals, is still obscure. Therefore, we examined the role of HDL in the regulation of corticosteroidogenesis in bovine adrenals in order to clarify whether or not HDL was selectively utilized for corticosteroid synthesis in vitro. The present data demonstrated that HDL and LDL increased cortisol production in a dose-dependent manner in bovine adrenocortical cells in vitro, and also that HDL cholesterol increased cortisol production significantly higher than LDL cholesterol did. Addition of adrenocorticotrophic hormone (ACTH) with HDL to the incubation media enhanced much higher cortisol production than that with LDL in short time incubation. The present data also demonstrated that uptake of 125I-HDL was significantly greater than that of 125I-LDL. Thus, HDL rather than LDL is thought to be the preferred lipoprotein as a source of steroidogenic substrate cholesterol in bovine adrenal fasciculo-reticularis cells. |
| Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease Cutler, R. G., J. Kelly, et al. (2004), Proc Natl Acad Sci U S A 101(7): 2070-5. Abstract: Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid beta-peptide (Abeta) and degeneration of neurons in brain regions such as the hippocampus, resulting in progressive cognitive dysfunction. The pathogenesis of AD is tightly linked to Abeta deposition and oxidative stress, but it remains unclear as to how these factors result in neuronal dysfunction and death. We report alterations in sphingolipid and cholesterol metabolism during normal brain aging and in the brains of AD patients that result in accumulation of long-chain ceramides and cholesterol. Membrane-associated oxidative stress occurs in association with the lipid alterations, and exposure of hippocampal neurons to Abeta induces membrane oxidative stress and the accumulation of ceramide species and cholesterol. Treatment of neurons with alpha-tocopherol or an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and cholesterol and protects them against death induced by Abeta. Our findings suggest a sequence of events in the pathogenesis of AD in which Abeta induces membrane-associated oxidative stress, resulting in perturbed ceramide and cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that leads to clinical disease. |
| Involvement of phospholipase A2 in the supply of fatty acids required for cholesterol esterification associated with uptake of oxidized low-density lipoprotein in macrophages Akiba, S. (2003), Yakugaku Zasshi 123(10): 845-53. Abstract: The formation of foam cells, a critical event in the early stages of atherosclerosis, is associated with the uptake of oxidized low-density lipoprotein (oxLDL) by macrophages and the subsequent accumulation of cholesterol ester formed by the catalytic action of acyl-CoA: cholesterol acyltransferase (ACAT). Although free cholesterol, a substrate for ACAT, is supplied from the intracellular cholesterol pool, little is known about the pathways involved in the supply of fatty acids, precursors for fatty acyl-CoA as another substrate for ACAT. Our recent studies were undertaken to examine the possible involvement of phospholipase A2 (PLA2) in the supply of fatty acids required for the cholesterol esterification. In mouse peritoneal macrophages and RAW264.7 macrophages, oxLDL induced the liberation of fatty acids from membrane phospholipids to increase cholesterol ester having the fatty acids as an acyl chain. The changes in these lipids were suppressed by the inhibition of cytosolic PLA2 (cPLA2). Although oxLDL did not affect the activity or amounts of cPLA2, preincubation with oxLDL enhanced the release of fatty acids induced by Ca2+ ionophore, which accelerates the hydrolytic action of cPLA2. We further observed that oxLDL induced the generation of ceramide through the de novo synthesis. Exogenous ceramide and 13-hydroxyoctadecadienoic acid, an oxidized lipid in oxLDL particles, also stimulated fatty acid release. Based on these findings, we propose that oxLDL activates cPLA2 to supply fatty acids required for the cholesterol esterification, through the acceleration of the hydrolytic action of cPLA2 by endogenous ceramide and by oxidized lipids in oxLDL particles in macrophages. |
| Involvement of semicarbazide-sensitive amine oxidase-mediated deamination in atherogenesis in KKAy diabetic mice fed with high cholesterol diet Yu, P. H., M. Wang, et al. (2002), Diabetologia 45(9): 1255-62. Abstract: AIMS/HYPOTHESIS: Semicarbazide-sensitive amine oxidase has been recognised to be a potential risk factor in vascular disorders associated with diabetic complications and to be related to mortality in patients suffering from heart disease. This enzyme, associated with the vascular system, catalyses the deamination of methylamine and aminoacetone, and also acts as an adhesion molecule related to leucocyte trafficking and inflammation. The deaminated products include the toxic aldehydes, formaldehyde and methylglyoxal, respectively, hydrogen peroxide and ammonia. MATERIALS AND METHODS: In this study, the KKAy mouse, a strain possessing features closely resembling those of Type II (non-insulin-dependent) diabetes mellitus has been used to substantiate the hypothesis. Vascular lesions were induced via chronic feeding of a high cholesterol diet. RESULTS: Both MDL-72974A, a selective mechanism-based semicarbazide-sensitive amine oxidase inhibitor and aminoguanidine effectively inhibited aorta semicarbazide-sensitive amine oxidase activity, and caused a substantial increase in urinary methylamine, and a decrease in formaldehyde and methylgloxal levels. Inhibition of semicarbazide-sensitive amine oxidase also reduced oxidative stress, as shown by a reduction of malondialdehyde excretion. Both MDL-72974A and aminoguanidine reduced albuminuria, proteinuria and the number of atherosclerotic lesions in animals fed with a cholesterol diet over a period of treatment for 16 weeks. CONCLUSION/INTERPRETATION: Increased semicarbazide-sensitive amine oxidase-mediated deamination could be involved in the cascade of atherogenesis related to diabetic complications. |
| Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by bifidobacteria Tahri, K., J. P. Grill, et al. (1997), Curr Microbiol 34(2): 79-84. Abstract: To determine the conditions of cholesterol assimilation,various strains of Bifidobacterium species were cultured in the presence of cholesterol and bile salts. During culturing, Bifidobacterium breve ATCC 15700 assimilates cholesterol in the presence of oxgall at pH values lower than 6. This strain was selected to study the influence of conjugated (taurocholic acid) and deconjugated (cholic acid) bile salts on cholesterol assimilation. B. breve ATCC 15700 assimilated cholesterol(up to 51%) when cultures were undertaken in the presence of taurocholic acid, whereas less than 13% of the initial amount ofcholesterol was measured in the cells in the presence of cholic acid.Cultured in the presence of six individual di- or trihydroxyconjugated bile salts, bifidobacteria strains assimilated cholesterol. This assimilation appeared to be more important in the presence of trihydroxyconjugated bile salts (tauro- and glycocholic acids). It is concluded thattrihydroxyconjugated bile salts are involved in the assimilation of cholesterol by bifidobacteria. |
| Ion channel behavior of amphotericin B in sterol-free and cholesterol- or ergosterol-containing supported phosphatidylcholine bilayer model membranes investigated by electrochemistry and spectroscopy Huang, W., Z. Zhang, et al. (2002), Biophys J 83(6): 3245-55. Abstract: Amphotericin B (AmB) is a popular drug frequently applied in the treatment of systemic fungal infections. In the presence of ruthenium (II) as the maker ion, the behavior of AmB to form ion channels in sterol-free and cholesterol- or ergosterol-containing supported phosphatidylcholine bilayer model membranes were studied by cyclic votammetry, AC impedance spectroscopy, and UV/visible absorbance spectroscopy. Different concentrations of AmB ranging from a molecularly dispersed to a highly aggregated state of the drug were investigated. In a fixed cholesterol or ergosterol content (5 mol %) in glassy carbon electrode-supported model membranes, our results showed that no matter what form of AmB, monomeric or aggregated, AmB could form ion channels in supported ergosterol-containing phosphatidylcholine bilayer model membranes. However, AmB could not form ion channels in its monomeric form in sterol-free and cholesterol-containing supported model membranes. On the one hand, when AmB is present as an aggregated state, it can form ion channels in cholesterol-containing supported model membranes; on the other hand, only when AmB is present as a relatively highly aggregated state can it form ion channels in sterol-free supported phosphatidylcholine bilayer model membranes. The results showed that the state of AmB played an important role in forming ion channels in sterol-free and cholesterol-containing supported phosphatidylcholine bilayer model membranes. |
| Ion channels, membrane lipids and cholesterol: a role for membrane lipid domains in arterial function Tulenko, T. N., R. Bialecki, et al. (1990), Prog Clin Biol Res 334: 187-203. |
| Ionized and total magnesium levels in cyclosporin-treated renal transplant recipients: relationship with cholesterol and cyclosporin levels Markell, M. S., B. T. Altura, et al. (1993), Clin Sci (Lond) 85(3): 315-8. Abstract: 1. Ionized magnesium, measured using a newly developed ion-selective electrode, total magnesium, and ionized and total calcium were evaluated in 39 stable, long-term, cyclosporin-treated renal transplant recipients and compared with those of age-matched, non-transplanted control subjects. Total cholesterol, cyclosporin trough level, serum creatinine, time after-transplant and the ratio of ionized calcium to ionized magnesium were also measured in renal transplant recipients and the relationships between these variables and ionized and total magnesium were evaluated. 2. Renal transplant recipients exhibited marked deficits in ionized magnesium, with a mean value of 0.54 +/- 0.01 mmol/l as compared with 0.61 +/- 0.006 mmol/l for normal control subjects (P < or = 0.05), with a more moderate deficit in total magnesium. Values for ionized and total calcium did not differ. By stepwise linear multiple regression analysis, ionized magnesium was significantly related to cyclosporin trough level and total cholesterol but not to serum creatinine, time after transplant or the dose of cyclosporin. Ionized magnesium correlated inversely with cyclosporin trough level and directly with total cholesterol. The ratio of ionized calcium to ionized magnesium was elevated in renal transplant recipients when compared with control subjects and correlated positively with the cyclosporin trough level. 3. Deficits in ionized magnesium are common during the late post-transplant period in cyclosporin-treated renal transplant recipients. Ionized magnesium may be a more sensitive clinical parameter than total magnesium in this population, in whom total magnesium may be only mildly decreased in the setting of a severe deficit in ionized magnesium. 4. Ionized magnesium correlates with the cyclosporin level.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Ionizing radiation alters hepatic cholesterol metabolism and plasma lipoproteins in Syrian hamster Feurgard, C., N. Boehler, et al. (1999), Int J Radiat Biol 75(6): 757-66. Abstract: PURPOSE: The investigation of the effects of ionizing radiation on hepatic cholesterol metabolism and the concentration and composition of plasma lipoproteins in the male Syrian hamster. MATERIALS AND METHODS: After sublethal whole-body 60Co gamma-irradiation (8 Gy, 1 Gy/min), plasma lipoproteins were separated by density-gradient ultracentrifugation. Activities of hydroxymethylglutarylCoA (HMGCoA) reductase and of cholesterol 7alpha-hydroxylase were measured in hepatic microsomes and the low-density lipoprotein (LDL) receptor mass was determined in hepatic total membranes. Lipid peroxidation in LDL was assessed in vitro as the formation of conjugated dienes at 234 nm. A group of pair-fed animals served as controls as the food intake was markedly decreased with exposure to radiation. RESULTS: Plasma lipid concentrations decreased 2 days post-irradiation and then markedly increased by day 6 post-irradiation; plasma cholesterol was increased by 77% and triglycerides by +207%. LDL accumulated in plasma while high-density lipoprotein (HDL) levels decreased. HDL contained significant amounts of apo SAA, the acute phase apolipoprotein. The activities of hepatic HMGCoA reductase, the rate-limiting enzyme for cholesterol synthesis, increased (+125%, p=0.06); hepatic cholesterol 7alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, decreased (-85%); and the hepatic LDL receptor mass also decreased (-44%). The susceptibility of LDL to oxidation was also increased when animals were exposed to radiation. CONCLUSIONS: Lipoprotein modifications that appeared following radiation exposure may result from an induced inflammatory state and may further contribute to vascular damage. |
| IR and turbidity studies of vitamin E-cholesterol-phospholipid membrane interactions Severcan, F., N. Kazanci, et al. (1995), Biosci Rep 15(4): 221-9. Abstract: Binary and tertiary mixture of alpha-tocophenol, cholesterol and dimyristoylphosphatidylcholine in the form of multilamellar liposomes were investigated by Fourier Transform Infrared and visible spectroscopy. Results of the FTIR and turbidity experiments indicate that alpha T decreases or diminishes the effect of cholesterol on the frequency and the bandwidth of the C-H stretching, CH2 scissoring and C = O stretching bands in FTIR spectra and the turbidity measurements (recorded as absorbance values at 440 nm) in phospholipid model membranes. |