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Biomedical subjects

U Diczfalusy

Publications and source records attributed to U Diczfalusy.

At least 55 records · Page 3Linked to original sources
PubMed1996

The oxysterols cholest-5-ene-3 beta,4 alpha-diol, cholest-5-ene-3 beta,4 beta-diol and cholestane-3 beta,5 alpha,6 alpha-triol are formed during in vitro oxidation of low density lipoprotein, and are present in human atherosclerotic plaques.

Isolated human low density lipoprotein (LDL) was oxidized with either cupric ions or soybean lipoxygenase and linoleic acid. Cholesterol oxidation products (oxysterols) were determined by isotope dilution gas chromatography-mass spectrometry. A new cholestane-3,5,6-triol isomer, cholestane-3 beta,5 alpha,6 alpha-triol, which has not previously been recognized as a cholesterol autoxidation product, was found at similar concentrations as the well-known cytotoxic cholestane-3 beta,5 alpha,6 beta-triol during both copper- and lipoxygenase-mediated LDL oxidation. Furthermore, two epimeric cholest-5-ene-3 beta,4-diols were identified in the oxidized LDL at similar concentrations. These two isomers were also identified in human atherosclerotic tissue in a ratio of 1:1 at a concentration more than 10-times higher than in non-atherosclerotic vessels. In vitro oxidation of LDL under an 18O2 atmosphere revealed that molecular oxygen was the only source of the oxygen functions at C-4 in the cholest-5-ene-3 beta,4-diols. Taken together, these findings suggest that the cholest-5-ene-3 beta,4-diols in atherosclerotic plaques are formed by autoxidation.

Arteriosclerosis↗
PubMed1996

Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.

The presence of oxysterols in macrophages isolated from atherosclerotic tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, freshly isolated from atherosclerotic aorta, show about the same distribution of oxysterols, analyzed by isotope dilution mass spectrometry, except that all three preparations of human arterial-derived macrophages contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL expression, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on macrophage LPL mRNA expression compared with control. LPL activity in the medium was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier observation of a low level of LPL mRNA in arterial foam cells.

Animals↗
PubMed1996

Importance of a novel oxidative mechanism for elimination of intracellular cholesterol in humans.

We have recently demonstrated that cultured human alveolar macrophages efficiently convert cholesterol into excretable 27-oxygenated products. We show here that increasing the intracellular concentration of cholesterol by a factor of 10 leads to about a twofold increase in the excretion of 27-oxygenated products from cultured macrophages. Inhibition of the sterol 27-hydroxylase caused a significant intracellular accumulation of cholesterol. A direct comparison was made between flux of cholesterol and 27-oxygenated products from macrophages preloaded with [4-14C]cholesterol. Under the specific conditions employed with fetal calf serum in the culture medium, the flux of 27-oxygenated products was about 10% of that of cholesterol. Since the sterol 27-hydroxylase, which converts cholesterol to 27-oxygenated products, is present in many cell types, we suggest that 27-oxygenation is a general mechanism for removal of intracellular cholesterol. To evaluate this hypothesis, we measured the net uptake by the human liver of circulating 27-oxygenated products, which was found to be about 20 mg/24 h. This uptake corresponds to approximately 4% of the bile acid production, assuming quantitative conversion into bile acids. It is concluded that the 27-hydroxylase pathway is of significance for elimination of extrahepatic cholesterol.

Cells, Cultured↗
PubMed1996

Formation of oxysterols during oxidation of low density lipoprotein by peroxynitrite, myoglobin, and copper.

Oxidation of low density lipoprotein (LDL) in the artery wall leads to the formation of cholesterol oxidation products that may result in cytotoxicity. Different mechanisms could contribute to LDL oxidation in vivo resulting in characteristic and specific modification of the cholesterol molecule. Alternatively, attack on cholesterol by chain propagating peroxyl radicals could result in the same distribution of oxidation products irrespective of the initial pro-oxidant mechanism. To distinguish between these possibilities we have monitored the formation of nine oxysterols during LDL oxidation, promoted by copper, myoglobin, peroxynitrite, or azo bis amidino propane. Regardless of the oxidant used, the pattern of oxysterol formation was essentially the same. The yields of products identified decreased in the order 7-oxocholesterol > 7 beta-hydroxycholesterol > 7 alpha-hydroxycholesterol > 5,6 beta-epoxycholesterol > 5,6 alpha-epoxycholesterol except in the case of peroxynitrite in which case a higher yield of 5, 6 beta-epoxycholesterol relative to 7-oxocholesterol was found. No formation of cholestane 3 beta, 5 alpha, 6 beta-triol, or the 24-,25-,27-hydroxycholesterols was seen. Concentration of 7-oxocholesterol levels in LDL was positively correlated with the degree of protein modification. Endogenous alpha-tocopherol in LDL or supplementation with butylated hydroxytoluene prevented oxysterol formation. Taken together these data indicate that the oxidation of cholesterol and protein in LDL occur as secondary oxidation events consequent on the attack of fatty acid peroxyl/alkoxyl radicals on the 7-position of cholesterol, and with amino acids on apoB. Furthermore, oxidant processes with atherogenic potential, such as peroxynitrite, copper, and myoglobin are capable of producing oxidized LDL containing cytotoxic mediators.

Amidines↗
PubMed1996

Novel pathways for elimination of cholesterol by extrahepatic formation of side-chain oxidized oxysterols.

Recently, we described a new pathway whereby peripheral cells can eliminate intracellular cholesterol by conversion into the more polar oxysterols 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid. The latter steroids are easily excreted from the cells and transported to the liver for conversion into bile acids. Our attempts to evaluate the importance of this new mechanism are reviewed here and also our investigations on the possible presence of additional similar pathways for removal of extrahepatic cholesterol. Human alveolar macrophages in culture were shown to have a high capacity to convert cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid and to excrete these steroids into the culture medium. Treatment of the macrophages with cyclosporin A, an inhibitor of sterol 27-hydroxylase, reduced the excretion of the 27-hydroxylated products by more than 90%, with a concomitant accumulation of intracellular cholesterol. The quantitative importance of the mechanism in relation to reverse cholesterol transport was investigated in 14C-cholesterol labelled macrophages exposed to HDL. At very low concentrations of HDL, possibly similar to those present in tissues, the two pathways were about equally effective. At optimal concentrations of HDL, however, reverse cholesterol transport was about 10-fold more effective than the sterol 27-hydroxylase pathway. The net uptake of 27-oxygenated steroids by the liver was measured in volunteers by comparison of the levels in the hepatic vein with those in a peripheral artery. Approximately 20 mg of 27-oxygenated oxysterols was taken up by the liver during 24 hours. Quantitative conversion of these oxysterols into bile acids would correspond to 4% of the total bile acid formation. It is evident that this new pathway contributes significantly to cholesterol elimination. The possibility that the sterol 27-hydroxylase pathway is of importance for cholesterol homeostasis in the brain was investigated by measuring oxysterols in the internal jugular vein and in an artery of healthy volunteers. There was no net flux of 27-hydroxycholesterol from the brain into the circulation. There was, however, a significant flux of 24-hydroxycholesterol, corresponding to elimination of about 4 mg cholesterol/24 hours. This flux is higher than the estimated rate of synthesis of cholesterol in the human brain. To summarize, we have demonstrated two mechanisms for cholesterol elimination from extrahepatic cells by specific oxygenases capable of oxidizing the steroid side-chain. The efficiency of these mechanisms is based on the fact that side-chain hydroxylated cholesterol species are both translocated through lipophilic membranes and converted into bile acids at a much faster rate than cholesterol itself. The importance of the sterol 27-hydroxylase-mediated mechanism is illustrated by the fact that patients who lack this enzyme develop xanthomas and premature atherosclerosis in spite of normal levels of circulating cholesterol.

Cholesterol↗
PubMed1995

Clofibrate treatment increases stearoyl-CoA desaturase mRNA level and enzyme activity in mouse liver.

Stearoyl-CoA desaturase activity is encoded by two highly homologous genes, SCD1 and SCD2, which show tissue-specific expression and regulation. SCD1, which is expressed in the liver, showed a marked diurnal variation with the highest expression during the feeding period. Treatment of mice with the peroxisome proliferator clofibrate, which induces several lipid metabolizing enzymes, increased both the enzyme activity and mRNA level in the liver, indicating regulation at the transcriptional level. The highest expression of both SCD1 and SCD2 was found in brown adipose tissue, which was slightly down-regulated by feeding a fat-free diet.

Adipose Tissue, Brown↗
PubMed1995

Time course of oxysterol formation during in vitro oxidation of low density lipoprotein.

Cholesterol oxidation products (oxysterols) have been implicated in several aspects of atherogenesis; they affect key enzymes in cholesterol homeostasis, induce calcification in vascular cells and possess cytotoxic properties. Oxysterols are formed during oxidative modification of low density lipoprotein (LDL). Using a recently developed method based on isotope dilution-mass spectrometry, the kinetics of formation of oxysterols during oxidation of LDL by cupric ions or soybean lipoxygenase was studied. The same products, mainly 7- and 5-oxygenated cholesterol, were formed by the two oxidation methods. Virtually no side-chain oxidized oxysterols were formed. During the oxidations, preferentially esterified cholesterol was consumed and consumption of polyunsaturated fatty acids and formation of conjugated dienes preceded the appearance of oxysterols. Cholesterol 7-hydroperoxides potential cytotoxins, were present in LDL oxidized by copper or lipoxygenase.

Cholesterol↗
PubMed1995

Determination of cholesterol oxidation products in human plasma by isotope dilution-mass spectrometry.

A method based on isotope dilution-mass spectrometry was developed for the determination of nine cholesterol oxidation products in human plasma. The cholesterol oxidation products determined were cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol (7 alpha- and 7 beta-hydroxycholesterol, respectively), 3 beta-hydroxycholest-5-en-7-one(7-oxocholesterol),5,6 alpha-epoxy-5 alpha- cholestan-3 beta-ol (cholesterol-5 alpha,6 alpha-epoxide),5,6 beta-epoxy-5 beta-cholestan-3 beta-ol (cholesterol-5 beta,6 beta-epoxide), (cholesterol-5 beta,6 beta-epoxide), cholestane-3 beta,5 alpha,6 beta-triol, cholest-5-ene-3 beta,24-diol (24-hydroxycholesterol), cholest-5-ene-3 beta,25-diol (25-hydroxycholesterol), and cholest-5-ene-3 beta,27-diol (27-hydroxycholesterol). A corresponding deuterium-labeled internal standard, containing 3 to 6 deuterium atoms, was synthesized for each cholesterol oxidation product except 5 beta,6 beta-epoxycholesterol which was determined using the internal standard for 5 alpha,6 alpha-epoxycholesterol. Plasma from 31 healthy volunteers was analyzed by the new method and 27-, 24-, and 7 alpha-hydroxycholesterol were the most abundant cholesterol oxidation products (mean values 154, 64, and 43 ng/ml, respectively). The other oxysterols determined were present in concentrations lower than 30 ng/ml. Males had higher 27-hydroxycholesterol concentrations in plasma than females. The 5,6-oxygenated products were present mainly unesterified while the other oxidation products were mostly in esterified form.

Cholesterol↗
PubMed1994

Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages.

27-Hydroxycholesterol was found in surprisingly high amounts in atherosclerotic human femoral arteries. When human macrophages were cultured in a medium containing serum, there was a significant transfer of 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholestenoic acid from the cells into the medium. Sterol 27-hydroxylase (EC 1.14.13.15) is likely to be responsible for formation of the two products as shown by use of immunoblotting, a specific inhibitor, and the 18O-labeling technique. Sterol 27-hydroxylase has the unusual ability to hydroxylate the same methyl group three times to give a carboxylic acid; thus, 3 beta-hydroxy-5-cholestenoic acid is likely to be a direct product of the enzyme. The production of these steroids increased after addition of cholesterol to the culture medium. By using deuterium-labeled cholesterol, it was ascertained that most of the oxidized products were formed from exogenous cholesterol taken up by the cells. 27-Hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid are present in the circulation and are efficiently converted into bile acids in human liver. It is suggested that conversion of cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid represents a general defence mechanism for macrophages and possibly also other peripheral cells exposed to cholesterol. Absence of this defence mechanism may contribute to the premature atherosclerosis known to occur in patients with sterol 27-hydroxylase deficiency (cerebrotendinous xanthomatosis).

Aged↗
PubMed1994

Molecular cloning and identification of a rat serum carboxylesterase expressed in the liver.

We have cloned and sequenced a carboxylesterase from rat liver and purified the corresponding protein from rat blood. The cDNA encodes the entire mature serum esterase protein. It is apparently identical to cDNAs cloned from rat liver by several groups (Long, R. M., Satoh, H., Martin, B. M., Kimura, S., Gonzales, F. J., and Pohl, L. R. (1988) Biochem. Biophys. Res. Commun. 156, 866-873; Takagi, Y., Morohashi, K.-i., Kawabata, S.-i., Go, M., and Omura, T. (1988) J. Biochem. (Tokyo) 104, 801-806; and Robbi, M., and Beaufay, H. (1992) Biochem. Biophys. Res. Commun. 183, 836-841). However, the identification of the protein encoded by this cDNA has not been previously reported. The COOH-terminal -TEHT sequence found in the rat serum carboxylesterase does not possess retention properties and is therefore responsible for its secretion and presence in the circulation. The rat serum carboxylesterase was purified to apparent homogeneity by affinity chromatography on immobilized antibody to rat liver microsomal acyl-CoA thioesterase followed by ion exchange chromatography. The purified protein, with a M(r) of approximately 70,000, was cleaved in situ in a polyacrylamide gel with trypsin, and two peptides were isolated and sequenced. Sequence analysis showed that both peptides were identical only to the corresponding deduced amino acid sequence of the cloned cDNA. Antibodies raised to the COOH-terminal amino acid sequence deduced from the cDNA cross-reacted with the purified rat serum carboxylesterase. Changes in serum esterase activity levels followed changes in protein mass in rat serum and changes in liver mRNA levels in response to various nutritional conditions while total liver esterase activity was essentially unchanged. The above experiments confirm the identity of the protein isolated from rat sera with the cDNA cloned from rat liver and suggest a function for the serum esterase in lipid metabolism.

Amino Acid Sequence↗
PubMed1994

Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study.

In several studies diets supplemented with fish oil containing a high proportion of omega-3-polyunsaturated fatty acids (w-3-PUFA) have been shown to produce beneficial effects, such as a reduction in blood pressure, lipid levels and inflammation, all of which may affect the course of IgA nephropathy. However, the results of hitherto published studies concerning IgA nephropathy have been inconclusive. We therefore carried out a prospective, randomized, placebo-controlled six-month study with a higher daily dose of w-3-PUFA than used in previous studies. Thirty-two adult patients with biopsy-proven IgA nephropathy and proteinuria completed the study: 15 were assigned to a fish-oil product with a high percentage of w-3-PUFA (K 85, with 55% eicosapentenoic and 30% docosahexenoic acid) and 17 to corn oil, 6g daily of either oil. At the start, no significant differences were found between the two groups (K85: 3 females/12 males, mean age 39 years (range 22-64), corn oil: 4 females/13 males, age 42 years (range 26-68). By six months, supplements of K85 resulted in a slight but significant reduction in glomerular filtration rate (GFR) compared to the start: 51Cr-EDTA: 63 +/- 22 to 59 +/- 21 ml/min/1.73 m2 (p < 0.05), creatinine clearance: 91 +/- 31 to 79 +/- 25 ml/min (p < 0.01), s-creatinine: 131 +/- 39 to 139 +/- 39 mumol/l, whereas no change in GFR was observed in the corn oil group. The urinary total protein and red blood cell excretions were not affected in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Peroxisomal chain-shortening of thromboxane B2: evidence for impaired degradation of thromboxane B2 in Zellweger syndrome.

We have shown that rat liver peroxisomes can chain-shorten prostaglandins to dinor- and tetranor-metabolites. In a recent in vivo study we could demonstrate that peroxisomes are of major importance for chain-shortening of prostaglandin F2 alpha in humans (1991, Diczfalusy et al. J. Clin. Invest. 88:978-984). This was shown by identifying the major urinary metabolites of radiolabeled prostaglandin F2 alpha given intravenously to a patient lacking functional peroxisomes (Zellweger syndrome). In the present investigation we have studied the peroxisomal chain-shortening of thromboxane B2, a compound structurally related to prostaglandins. Isolated rat liver peroxisomes oxidized thromboxane B2 to a chain-shortened metabolite in an NAD(+)-dependent reaction. The metabolite was identified as 9,11,15-trihydroxy-2,3,4,5-tetranor-thromb-13-enoic acid (tetranor-thromboxane B1). The urinary excretion of the major beta-oxidized metabolites of thromboxane B2 and prostacyclin was determined in three Zellweger patients and six age-matched controls. The controls excreted on an average 1.7 and 1.1 ng/mg creatinine of 2,3-dinorthromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, respectively. In none of the three Zellweger patients could these dinor-metabolites be detected, i.e., the urinary excretion was less than 0.2 ng/mg creatinine. This shows that peroxisomes play an important role in the degradation of the carboxyl side chain of thromboxane B2 in vivo.

Animals↗
PubMed1992

On the mechanism of oxidation of cholesterol at C-7 in a lipoxygenase system.

Incubation of [7-2H2]cholesterol with soybean lipoxygenase and linoleic acid in the presence of oxygen gave a mixture of 5-cholestene-3 beta,7 alpha-diol, 5-cholestene-3 beta,7 beta-diol, 3 beta-hydroxy-5-cholesten-7-one,5 alpha,6 alpha-epoxycholestan-3 beta-ol, and 5 beta,6 beta-epoxycholestan-3 beta-ol. The conversion into the 7-oxygenated products was associated with a very high intermolecular isotope effect (KH/KD = 15-17), suggesting that the rate-limiting step in the overall conversion is likely to be the abstraction of hydrogen at C-7 in a radical reaction. Evidence that linoleic acid is to some extent directly involved was obtained with the use of [7-3H]cholesterol. Incubation of [7-3H]cholesterol resulted in a significant incorporation of 3H in the reisolated linoleic acid fraction. The isotope effect associated with conversion of [7 alpha-2H]cholesterol into 7-oxygenated products in the lipoxygenase system was 2-3, indicating that the extraction of hydrogen is nonstereospecific. Incubation of [7-2H2]cholesterol with 13-hydroperoxy-9,11-octadecadienoic acid gave the above 7-oxygenated products with relatively small isotope effects (KH/KD = 3-4). It is concluded that the most important mechanism for oxidation of cholesterol at C-7 in the lipoxygenase system involves participation of radicals and that a carbon-centered linoleic acid radical can extract hydrogen directly from cholesterol. Fatty acid hydroperoxides and their secondary products seem to be less important as initiators in connection with oxidation of cholesterol.

Cholesterol↗
PubMed1991

Impaired intrarenal dopamine production following intravenous sodium chloride infusion in type 1 (insulin-dependent) diabetes mellitus.

Type 1 (insulin-dependent) diabetes mellitus is characterized by impaired sodium excretion following NaCl infusion. To investigate the possible role of dopamine in the impaired natriuresis in diabetes, intrarenal sodium handling, sodium excretion and urinary dopamine output, reflecting intrarenal dopamine formation, were studied following a 2 h 0.9% NaCl infusion (25 ml/kg) in eight diabetic patients and nine control subjects. The increase in sodium excretion in response to NaCl infusion was significantly (p less than 0.01) reduced in diabetic patients (19 +/- 7%) as compared with control subjects (46 +/- 8%). Fractional proximal tubular sodium reabsorption (determined by lithium clearance) decreased in the control group (p less than 0.01) following NaCl infusion but not in the diabetic group. Fractional distal tubular reabsorption decreased similarly in both groups. In response to NaCl urinary dopamine excretion increased by approximately 15% (p less than 0.01) in the control group but did not change in the diabetic group. The mean urinary dopamine excretion above basal was significantly greater in the control group (8.4 +/- 2.1 nmol/h) than in the diabetic group (-2.2 +/- 2.1 nmol/h; p less than 0.01). The urinary sodium/dopamine excretion ratio did not differ significantly between the two groups in the basal state or following NaCl. Baseline plasma levels of atrial natriuretic peptide did not differ between control and diabetic patients. In the control group atrial natriuretic peptide levels increased significantly (p less than 0.01) in response to NaCl whereas atrial natriuretic peptide levels did not change in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to beta-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [3H]prostaglandin F2 alpha to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK C18 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2 alpha metabolite from the Zellweger patient was identified as an omega-oxidized C20-prostaglandin, 9,11-dihydroxy-15-oxoprost-5-ene-1,20-dioic acid. The major urinary prostaglandin F2 alpha metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal beta-oxidation is of major importance for in vivo chain shortening of prostaglandins.

Chromatography, High Pressure Liquid↗
PubMed1990

Identification of intermediates in the peroxisomal beta-oxidation of linoleic acid.

Rat liver peroxisomes contain a beta-oxidation system different from that present in the mitochondria. Intermediates in this oxidation have not hitherto been identified by direct methods. Incubation of linoleic acid with isolated peroxisomes (in the absence of detergent) resulted in the accumulation of polar products in addition to the chain-shortened products. Omission of NAD in the incubation mixture considerably increased the accumulation of these products. Two of the products were isolated and characterized by gas chromatography-mass spectrometry. They were identified as 2,3-dehydrolinoleic acid and 3-hydroxylinoleic acid, based on identical chromatographic behaviour and mass spectra compared to synthetic reference compounds. Stereochemical analysis of catalytically hydrogenated 3-hydroxylinoleic acid showed a D/L ratio near to one. The mechanism behind the apparent lack of stereospecificity is discussed in relation to the recently described novel peroxisomal 2-enoyl-CoA hydratase (Smeland, T.E., Li, J., Chu, C.-h., Cuebas, D. and Schultz, H. (1989) Biochem. Biophys. Res. Commun. 160, 988-992 and Hiltunen, J.K., Palosaari, P.M. and Kunau, W.-H. (1989) J. Biol. Chem. 264, 13536-13540). In previous work we have demonstrated that beta-oxidation intermediates accumulate also in the peroxisomal metabolism of C27-bile acid intermediates and prostaglandins. The possibility is discussed that the peroxisomal beta-oxidation system is less tightly coupled than the corresponding system in mitochondria.

Animals↗
PubMed1990

Experimental atherosclerosis: effects of oestrogen and atherosclerosis on thromboxane and prostacyclin formation.

We evaluated the effect of oestrogen and experimental atherosclerosis on the in vivo formation of thromboxane and prostacyclin in rabbits. Twenty-four New Zealand White rabbits were divided into four groups. One group received control diet, one group received control diet and oestrogen, one group received control diet supplemented with 1% cholesterol and one group received cholesterol supplemented diet and oestrogen during 3 months. The in vivo formation of thromboxane and prostacyclin were measured as 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in urine by gas chromatography/mass spectrometry. All rabbits on cholesterol diet became hypercholesterolaemic and developed atherosclerosis. As in previous experiments cholesterol and oestrogen-treated rabbits had only minor atherosclerosis compared to purely cholesterol-fed rabbits. The in vivo production of thromboxane in oestrogen-treated rabbits decreased from 1641 +/- 162 pg mg-1 creatinine pretreatment to 808 +/- 92 pg mg-1 creatine at 12 weeks (P = 0.0001). In contrast, the in vivo production of prostacyclin increased during oestrogen treatment (P = 0.0027). The in vivo production of prostacyclin decreased during pure cholesterol feeding without oestrogen 1384 +/- 219 pg mg-1 creatinine to 702 +/- 142 pg mg-1 creatinine (P = 0.0091). The ratio of in vivo prostacyclin to thromboxane formation increased 2-3-fold during oestrogen therapy (P = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗