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At least 19 recordsLinked to original sources
PubMed1982

Sarcolemmal desmosterol accumulation and membrane physical properties in 20,25-diazacholesterol myotonia.

In rats treated biweekly with 20,25-diazacholesterol (200 mg/kg orally), the desmosterol level in skeletal muscle sarcolemma increased progressively to about 80% of membrane sterol while total sterol levels remained constant. Following a single oral dose of 20,25-D, the kinetics of desmosterol accumulation and subsequent loss in sarcolemma were more rapid than in whole muscle homogenates. The anisotropy of diphenylhexatriene fluorescence and the calculated microviscosity of the probe's microenvironment decreased significantly with increasing desmosterol levels in a temperature-dependent manner, although fluorescent lifetimes were not altered. Fluorescent probes which localize in more superficial regions of the membrane detected no change. Studies with erythrocyte ghost membranes yielded results comparable to sarcolemma. Replacement of membrane yielded results comparable to sarcolemma. Replacement of membrane cholesterol with desmosterol reduced the local microviscosity of membrane cholesterol with desmosterol reduced the local microviscosity of the membrane hydrophobic region associated with phospholipid acyl chains and sterol side chains, but had little apparent effect on more superficial, polar regions. These observations can be correlated with the membrane location of the unsaturated side chain in desmosterol.

Animals↗
PubMed1986

Selected ion monitoring technique for the evaluation of sterols in cerebrospinal fluid: a new approach to desmosterol test for central nervous system tumors.

The desmosterol test for the diagnosis of central nervous system (CNS) tumors is proposed in a simplified form. The procedure is based upon the analysis of sterol profile in cerebrospinal fluid (CSF) by selected ion monitoring (SIM) technique. Applied to 55 patients with tumoral and non tumoral CNS disease, the new test detects average levels of CSF desmosterol in tumor bearing patients that are tenfold higher than in the absence of CNS neoplasia. On an individual basis, a concentration of CSF desmosterol equal to or higher than the mean plus twice the standard deviation for the reference group of patients with no CNS tumor, is considered a positive result. Based on this criterion, a correct diagnosis was made in 73% of cases vs 77% of the former test, which required a 5-day treatment period with a desmosterol-reductase inhibitor in order to increase CSF desmosterol concentration. With this revised procedure CSF desmosterol can be detected in smaller volumes of CSF without any drug pretreatment, thus making the test more suitable for clinical application.

Brain Neoplasms↗
PubMed1989

The reactivity of desmosterol and other shellfish- and xanthomatosis-associated sterols in the macrophage sterol esterification reaction.

The acyl-CoA: cholesterol acyl transferase (ACAT) reaction in macrophages is a critical step in atherosclerotic foam cell formation, but little is known about the reaction's sterol substrate specificity. In this report we examine the macrophage ACAT reactivity of the shellfish sterol, desmosterol, and other sterols found in man because of shellfish ingestion or in association with the foam cell diseases sitosterolemia and cerebrotendinous xanthomatosis (CTX). We first show that the J774 macrophage, a foam cell model with a hyperactive ACAT pathway, synthesizes desmosterol instead of cholesterol and that both endogenous and exogenous desmosterol are substrates and stimulators of the ACAT reaction in these cells. When exogenous desmosterol was added to human monocyte-derived macrophages, ACAT was stimulated 29- and 4-fold compared with control and cholesterol-treated cells, respectively. Steryl ester mass accumulation in desmosterol-treated human macrophages was 10-fold greater than in control cells and 3-fold greater than in cholesterol-treated cells. Another shellfish sterol, 24-methylene cholesterol, also stimulated ACAT in human macrophages, but most of the xanthomatosis-related sterols did not stimulate ACAT. These data suggest that: (a) the shellfish sterols desmosterol and 24-methylene cholesterol may be atherogenic; and (b) the excessive foam cell formation seen in sitosterolemia and CTX cannot be explained by ACAT hyperreactivity of their associated sterols.

Animals↗
PubMed1976

Desmosterol in human and experimental brain tumors in tissue culture.

Desmosterol, a possible chemical indicator of brain tumors, was detected in cells of neurogenic, nitrosourea-induced rat tumors (neurinomas and gliomas, C6 cell line) and in human astrocytomas grown in lipid-poor media. A further increase in the amount of cell desmosterol was obtained when triparanol was added to media containing delipidized serum. Cholesterol was replaced almost completely by desmosterol in tumor cells grown in media containing nontoxic levels of 20,25-diazacholesterol. Desmosterol did not accumulate when these inhibitors of desmosterol-reductase were added to culture media containing cholesterol and other lipids (whole fetal calf serum). The results demonstrate that tumors of the nervous system grown in tissue culture are capable of sterol synthesis, and indicate that a central mechanism of cholesterol synthesis is operative in these cells, which may be related to the availability of exogenous cholesterol. It is concluded that these findings are relevant to clinical studies on the use of cholesterol inhibitors as tools for the detection of brain tumor activity.

Animals↗
PubMed1984

Membrane fluidity and myotonia: effects of cholesterol and desmosterol on erythrocyte membrane fluidity in rats with 20,25-diazacholesterol-induced myotonia and on phospholipid liposomes.

Previous spin-label and electromyographic experiments with rats fed 20,25-diazacholesterol, an inhibitor of the biosynthetic conversion of desmosterol to cholesterol, demonstrated an increased erythrocyte membrane fluidity and myotonia, a prolonged muscle contraction upon stimulation. The current studies with rats showed normal erythrocyte fluidity in animals fed 20,25-diazacholesterol but maintained on a high-cholesterol diet and no myotonia. Studies of model membrane systems composed of phospholipid vesicles containing desmosterol, cholesterol, or both demonstrated that desmosterol increased membrane lipid fluidity relative to cholesterol, suggesting that in 20,25-diazacholesterol-induced myotonia, in which desmosterol accounts for 85% of the plasma sterol, the increased membrane fluidity previously observed in erythrocytes and sarcolemma in this animal model of human congenital myotonia may be due to desmosterol.

Animals↗
PubMed1976

Binding of squalene, lanosterol, desmosterol, and cholesterol to proteins in brain and liver 105,000 g supernatant fractions: evidence for specific binding sites.

The binding of squalene, lanosterol, desmosterol, and cholesterol to proteins in 105,000 g supernatant fraction (S105) from brain and liver of rats was investigated. The S105 fractions from both tissues contain specific binding sites for sterols, which are sensitive to trypsin. The dissociation constants for squalene and sterol protein complexes were in the range of 10(-6) M and were not appreciably different for proteins in brain and liver S105. Competition studies revealed that both brain and liver S105 contain one receptor protein which binds lanosterol and is specific for methyl sterols, and a second receptor which binds both desmosterol and cholesterol. Binding of 7-dehydrocholesterol reported by others must occur at a third independent site since this compound does not interfere with the binding of lanosterol, desmosterol, or cholesterol. Although binding of squalene to proteins in brain and liver S105 does occur, we were unable to show the specificity of squalene binding. The concentration of desmosterol and cholesterol binding sites, which ranged from 6 to 10 nmol/mg protein, was 3- to 5-fold higher than the concentration of squalene and lanosterol binding sites (1.6-2.3 nmol/mg protein). The brain S105 from suckling rats contained fewer binding sites for desmosterol and cholesterol than the brain S105 from weaned rats. However, the concentration of lanosterol binding sites in brain S105 did not show an age-dependent change. The receptor proteins in brain and liver appear to be identical.

Animals↗
PubMed1975

Desmosterol accumulation in rats with experimental myotonia.

Desmosterol is found in various organs of rats that show signs of myotonia in their skeletal muscle as a result of treatment with 20.25-diazacholesterol. The amount of desmosterol depends on the time of treatment, and is different in different organs and different kinds of muscle. The increase in desmosterol is much lower and the rats do not show any signs of myotonia when fed a cholesterol rich diet in addition to treatment with 20.25-diazacholesterol. Treatment with triparanol also causes desmosterol accumulation but in these rats myotonia is rarely observed. Our results suggest that in the experimental animals myotonia becomes manifest when every second cholesterol molecule of the muscle cell membrane is replaced by desmosterol. This is easily achieved in animals fed with 20.25-diazacholesterol but rarely occurs with triparanol.

Animals↗
PubMed1972

In vivo demonstration of the cholesterol feedback system by means of a desmosterol suppression technique.

This report describes a "desmosterol suppression" technique with which it has been possible to demostrate the operation of the cholesterol negative feedback system in the intact animal. 0.1% triparanol in the diet causes a virtually complete block in the conversion of desmosterol to cholesterol by liver and intestine. Since desmosterol is not consumed in the diet, the level of plasma desmosterol can be employed as an index of endogenous sterol production and release into the bloodstream. With this technique it was shown that the feeding of cholesterol for 8 days to rats decreases blood desmosterol levels to less than 5% of control values. Very similar results were obtained when cholesterol synthesis was assayed in vivo with acetate-(14)C as a cholesterol precursor. These observations indicate that the cholesterol feedback system operates very effectively in the intact animal in suppressing the endogenous contribution to the circulating cholesterol pool. Since intestinal cholesterol synthesis is only slightly inhibited by exogenous cholesterol, these results also indicate that the intestine does not represent a significant source of plasma sterols in the rat.

Acetates↗
PubMed1983

Desmosterol in human milk.

Milk samples were collected from mothers at 2, 6, 12 and 16 weeks postpartum. Desmosterol was found to be present in all the milk samples. Identification of desmosterol was based on retention times with two gas liquid chromatography (GLC) columns and verified by GC-mass spectrometry. The concentration of desmosterol in breast milk increased significantly (P less than .05) from 0.6 mg/100 ml at 2 weeks to 1.3 mg/100 ml at 16 weeks postpartum. Desmosterol was not significantly correlated with total lipid, total cholesterol or free cholesterol in the milk.

Desmosterol↗
PubMed1989

Identification of cholesta-7,24-dien-3 beta-ol and desmosterol in hamster cauda epididymal spermatozoa.

The sterol composition of hamster cauda epididymal spermatozoa was remarkably different from that of several other mammalian spermatozoa. Desmosterol and cholesta-7,24-dien-3 beta-ol account for as much as 90% of the total sterols. Cholesterol and desmosterol are the major components of mouse cauda epididymal spermatozoa, and rabbit, boar and bull ejaculated spermatozoa. Cholesta-7,24-dien-3 beta-ol was not detected. Furthermore, cholesterol was the main sterol in hamster caput epididymal spermatozoa, while only a trace amount of desmosterol was detected and cholesta-7,24-dien-3 beta-ol was hardly detected at all. The sterol content of cauda and caput epididymal spermatozoa was 0.17 +/- 0.05 mumol/10(8) spermatozoa. During maturation, the desmosterol and cholesta-7,24-dien-3 beta-ol levels increase and the cholesterol level decreases. Cholesta-7,24-dien-3 beta-ol appears as a sterol in mature spermatozoa and seems to be a characteristic sterol of hamster cauda epididymal spermatozoa.

Animals↗
PubMed1983

Transfer of exogenous cholesterol to microsomes of hepatocytes investigated with [3H]desmosterol tracer.

The feasibility of using exogenous [3H]desmosterol as a mass metabolic tracer for exogenous non-esterified cholesterol in hepatocytes is investigated with albumin-bound non-esterified cholesterol containing [3H]desmosterol and [14C] cholesterol tracers. The amounts of uptake and metabolism of exogenous cholesterol monitored by either tracer are the same. In addition, the conversion of [3H]desmosterol into [3H]cholesterol by the delta 24-sterol reductase in the microsomes can be used as an estimate for the mass transfer of exogenous cholesterol to the microsomes. The results obtained indicate that only a small fraction of exogenous cholesterol that was transferred to the microsomes was metabolized into bile acids and steryl esters. The technique of estimating the mass transfer of exogenous cholesterol to the microsomes with [3H]desmosterol may be of importance in investigations dealing with the effect of exogenous plasma cholesterol on changes in the physiological functions of the endoplasmic reticulum in the cells.

Animals↗
PubMed1974

Restoration of the conversion of desmosterol to cholesterol in L-cells after hybridization with human fibroblasts.

Hybrids between different human cells (which synthesize cholesterol) and mouse cells (whose end-product of sterol synthesis is desmosterol) were analyzed for the ability to convert desmosterol to cholesterol. Conversion of [(14)C]desmosterol to cholesterol and incorporation of [(14)C]acetate into the end-product sterol were studied in the parental and hybrid cells. Concordant segregation of the conversion of desmosterol to cholesterol and the human chromosome F-20 was observed.

Acetates↗
PubMed1990

Oxygenation of desmosterol and cholesterol in cell cultures.

In order to determine whether hydration of the delta 24 bond of desmosterol contributes to the formation of the regulatory oxysterol, 25-hydroxycholesterol, [3H]desmosterol was incubated with two cultured cell lines and the labeled products were analyzed. Small amounts of 25-hydroxycholesterol were formed with Chinese hamster lung (Dede) cell cultures, but not with mouse fibroblast (L) cell cultures. Apparently, desmosterol was converted into cholesterol, a process that does not occur in L cells, before 25-hydroxycholesterol takes place. No reliable evidence could be obtained for hydration of the delta 24 bond or for the reverse reaction upon incubation of [3H]25-hydroxycholesterol. Oxygenation of desmosterol occurred in both Dede and L cell cultures to give a mixture of 24(R)- and 24(S)-25-epoxy-cholesterol. This reaction, along with the production of 7-oxygenated sterols, may account for low levels of HMG-CoA reductase repressor activity previously found to be associated with delta 24 sterols.

Animals↗
PubMed1993

Unique lipids of primate spermatozoa: desmosterol and docosahexaenoic acid.

Spermatozoa represent a tissue readily accessible for study after various exogenous perturbations. To characterize the lipid composition of monkey sperm and to establish a baseline from which dietary or pharmaceutical influences may then be evaluated, we collected semen samples from five rhesus monkeys by electroejaculation and analyzed the sperm for sterols, fatty acid composition, and the molecular species of the ethanolamine glycerophospholipids. Two sterols were identified: cholesterol, 41%, and desmosterol, 59% of total sterols. Desmosterol was found only in the free form. Cholesterol existed in three different forms: free, 60%; esterified, 20%; and sulfated, 20%. Docosahexaenoic acid (22:6, DHA) was almost the only n-3 fatty acid in sperm phospholipids, 24% of the total fatty acids. DHA was present mainly in phosphatidylcholine and phosphatidylethanolamine. Oleic and palmitic acids were the predominant monounsaturated and saturated fatty acids. The ethanolamine glycerophospholipids were separated into three subclasses: diacyl 49%, alkenylacyl 43%, and alkylacyl 8%. Thirteen molecular species were identified and quantified. The sn-1 position of these molecular species contained exclusively 16:0, 18:0, or 18:1. The sn-2 position contained n-3, n-6, and n-9, as well as saturated fatty acids. The molecular species having n-3 fatty acids in the sn-2 position contributed 43, 73, and 100% of the total in the diacyl, alkenylacyl, and alkylacyl subclasses, respectively. The presence of the unusual sterol, desmosterol, a cholesterol precursor not found in measurable quantities in any other tissue suggests an important functional and structural role for desmosterol in spermatozoa. The other unique lipids, cholesterol sulfate and the n-3 docosahexaenoic acid, may also have a significant role in the function of spermatozoa.

Animals↗
PubMed1997

Biochemical markers for puberty in the monkey testis: desmosterol and docosahexaenoic acid.

We previously reported that the sperm of rhesus monkeys and humans uniquely contain large amounts of desmosterol not found in other tissues and have a high concentration of the highly polyunsaturated n-3 fatty acid, docosahexaenoic acid (22:6 n-3). However, the lipid composition of the testis, from which sperm originate, is unknown. During puberty, the testis undergoes remarkable morphological changes as testosterone levels rise and sperm production begins. We hypothesized that testicular maturation might also involve dramatic changes in lipid composition. Accordingly, we characterized the sterol and fatty acid composition of the testis of rhesus monkeys throughout the lifespan, from birth to old age. Although the cholesterol content in the testis remained relatively unchanged throughout life, the desmosterol content first decreased from 59 microg/g in infants to 6 microg/g in prepubertal monkeys, increased to 83 microg/g during puberty, and reached a plateau of 248 microg/g in the young adult, where it remained into old age. The polyunsaturated fatty acid composition of the testis also changed markedly. Docosahexaenoic acid (22:6 n-3) increased from 5.1% of total fatty acids in infants and juveniles to 18.1% in postpubertal young adults. Although some n-6 fatty acids, arachidonic (20:4 n-6) and linoleic (18:2 n-6), decreased from 16.0% and 10.0% in prepubertal juveniles, respectively, to 7.1% and 3.3% in young adults; dihomogamma-linolenic acid (20:3 n-6), the precursor of 1 series PGs, increased greatly from 1.8% to 10.3%. Similar changes occurred in both membrane and storage lipids (phospholipids and triglycerides), respectively. After puberty, the testicular fatty acid pattern remained stable into old age. Our data demonstrated that puberty is accompanied by substantial changes in the lipid composition of the primate testis. These changes suggest that desmosterol and both n-3 and n-6 polyunsaturated fatty acids may have important roles in sexual maturation.

Aging↗
PubMed1978

Specific inhibition of desmosterol synthesis by ML--236B in mouse LM cells grown in suspension in a lipid-free medium.

The suspended growth of LM cells in a lipid-free chemically defined medium was almost completely inhibited in the presence of 0.1 microgram/ml of ML-236B, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate limiting enzyme in cholesterol biosynthesis in mammalian cells. This inhibition was effectively counteracted by adding a small amount of either mevalonate or cholesterol (dispersed in delipidated calf serum) to culture medium. The synthesis of desmosterol, the end product of sterol biosynthesis in LM cells, from [14C]acetate in cultured cells was highly sensitive to ML-236B, being inhibited 35 and 60% at its concentrations of 0.1 and 1 ng/ml, respectively, while the incorporation of [3H]mevalonate into desmosterol was not affected by ML-236B at concentrations up to 0.1 microgram/ml. Synthesis of fatty acids, phospholipids, triglycerides and macromolecules like DNA, RNA and protein were not suppressed by 10 microgram/ml of ML-236B. Desmosterol content of LM cells was reduced by treatment with ML-236B. These results indicate that ML-236B inhibited cell growth via specific interference in the pathway of sterol biosynthesis, presumably on the step catalyzed by HMG-CoA reductase.

Animals↗
PubMed1975

Desmosterol in rat central and peripheral nervous systems during normal and neoplastic growth.

Desmosterol (5, 24-cholestadien-3beta-ol; delta 24-cholesterol; 24-dehydrocholesterol), an immediate precursor of brain cholesterol, increased in malignant intracranial tumors induced in rats by nitrosourea derivatives. The average increase in desmosterol was higher in intracerebral gliomas than in neurinomas of the trigeminal nerve. Similarly, desmosterol increased only slightly in developing normal trigeminal nerve compared to the high levels observed in developing cerebrum. The differences may have been partly related to the predominantly growing cell type, i.e., glial (central nervous system) or Schwann (peripheral nervous system) cells seen at the time of study.

Age Factors↗
PubMedDate not supplied

[Isolation and identification of desmosterol and its concentration in animal brain tissue].

A method is developed for isolating desmosterol fro the brain of some animals. Sterols with Rf 0.37 and 0.51 are identified. Desmosterol is found in the brain unsaponifiable fraction of calves, piggies, chickens and rats. Its content in the mentioned animals brain is compared. Desmosterol content is shown to rise sharply in the rat brain during the first 12 days after birth. Interrelation between the level of sterols in the brain and formation of the nerve tissue myelin sheath is discussed.

Animals↗