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Biomedical subjects

J F Koster

Publications and source records attributed to J F Koster.

At least 55 records · Page 3Linked to original sources
PubMed1989

Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3.

In this study, we investigated the role of oxygen-derived free radicals and iron in mediating myocardial injury during ischemia and reperfusion. Iron is of special interest because it may enhance tissue injury during ischemia and reperfusion by catalyzing the formation of highly reactive hydroxyl radicals (by modified Haber-Weiss or Fenton reactions). Rat hearts, perfused by the Langendorff method, were subjected to global ischemia (15 minutes at 37 degrees C) and reperfusion. The effects of two iron chelators, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), and one antioxidant, (+)-cyanidanol-3, on contractile function, coronary flow, lactate dehydrogenase release, and lactate production were studied. The combination of these iron chelators is of special importance because L1 is known to prevent lipid peroxidation, induced by ADP/Fe3+ and NADPH in microsomes, in contrast to kojic acid. We found significant protection of contractile function (apex displacement) during reperfusion with 50 microM L1 and 20 microM (+)-cyanidanol-3 (p less than 0.01, n = 6), whereas no protection was found with 50 microM kojic acid (n = 6). Measurements of lactate dehydrogenase release during reperfusion showed a protective pattern similar to that found for heart contractile function, although 50 microM kojic acid also showed a significantly lower lactate dehydrogenase release during the first 10 minutes of reperfusion. No differences in coronary resistance or lactate release were found between the various groups. Our findings indicate that iron and oxygen-derived free radicals are important in the pathogenesis of postischemic reperfusion injury probably because of the formation of hydroxyl radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Endothelial lesions, dietary composition and lipid peroxidation.

The vascular endothelium can be regarded as a widely distributed organ with a pluripotent function in homeostasis and lipoprotein metabolism. There is now increasing evidence that the vascular endothelium is susceptible to oxygen radicals (oxidative stress). These radical molecules are capable of degrading the polyunsaturated acyl chains of membrane phospholipids (lipid peroxidation), hereby inducing pathologic changes in the underlying tissue. Since the fatty acid composition of our diet is reflected in the composition of cellular membranes, it is conceivable that their may be a relation between the dietary fatty acids and the tissue (endothelial) susceptibility towards lipid peroxidation. In addition, the occurrence of dietary antioxidant molecules (e.g., vitamin E) and trace elements (Se) may be important denominators of tissue protection against peroxidative processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Conditioned media of Kupffer and endothelial liver cells influence protein phosphorylation in parenchymal liver cells. Involvement of prostaglandins.

The possible role of Kupffer and endothelial liver cells in the regulation of parenchymal-liver-cell function was assessed by studying the influence of conditioned media of isolated Kupffer and endothelial cells on protein phosphorylation in isolated parenchymal cells. The phosphorylation state of three proteins was selectively influenced by the conditioned media. The phosphorylation state of an Mr-63,000 protein was decreased and the phosphorylation state of an Mr-47,000 and an Mr-97,000 protein was enhanced by these media. These effects could be mimicked by adding either prostaglandin E1, E2 or D2. Both conditioned media and prostaglandins stimulated the phosphorylase activity in parenchymal liver cells, suggesting that the Mr-97,000 phosphoprotein might be phosphorylase. Parenchymal liver cells secrete a phosphoprotein of Mr-63,000 and pI 5.0-5.5. The phosphorylation of this protein is inhibited by Kupffer- and endothelial-liver-cell media, and prostaglandins E1, E2 and D2 had a similar effect. The data indicate that Kupffer and endothelial liver cells secrete factors which influence the protein phosphorylation in parenchymal liver cells. This forms further evidence that products from non-parenchymal liver cells, in particular prostaglandin D2, might regulate glucose homoeostasis and/or other specific metabolic processes inside parenchymal cells. This stresses the concept of cellular communication inside the liver as a way by which the liver can rapidly respond to extrahepatic signals.

Animals↗
PubMed1988

Endotoxin stimulates glycogenolysis in the liver by means of intercellular communication.

Escherichia coli endotoxin (lipopolysaccharide) was shown to increase glycogenolysis in the perfused liver 2-3-fold. In isolated parenchymal liver cells, however, endotoxin did not influence glycogenolysis, whereas stimulation by endotoxin of glycogenolysis in the perfused liver could be blocked by aspirin. This suggests that the effect of endotoxin on liver glycogenolysis is mediated by eicosanoids. The amount of prostaglandin D2 (which is the major prostanoid formed by Kupffer cells) in the liver perfusates was increased 5-fold upon endotoxin addition, with a time course which preceded the increase in glucose output. It is concluded that endotoxin stimulates glycogenolysis in the liver by stimulating prostaglandin D2 release from Kupffer cells, with a subsequent activation of glycogenolysis in parenchymal liver cells. This mechanism of intercellular communication may be designed to provide the carbohydrate source of energy necessary for the effective destruction of invaded microorganisms, by phagocytic cells, including the Kupffer cells.

Animals↗
PubMed1988

Hormonal control of glycogenolysis in parenchymal liver cells by Kupffer and endothelial liver cells.

Conditioned media of isolated Kupffer and endothelial liver cells were added to incubations of parenchymal liver cells, in order to test whether secretory products of Kupffer and endothelial liver cells could influence parenchymal liver cell metabolism. With Kupffer cell medium an average stimulation of glucose production by parenchymal liver cells of 140% was obtained, while endothelial liver cell medium stimulated with an average of 127%. The separation of the secretory products of Kupffer and endothelial liver cells in a low and a high molecular weight fraction indicated that the active factor(s) had a low molecular weight. Media, obtained from aspirin-pretreated Kupffer and endothelial liver cells, had no effect on the glucose production by parenchymal liver cells. Because aspirin blocks prostaglandin synthesis, it was tested if prostaglandins could be responsible for the effect of media on parenchymal liver cells. It was found that prostaglandin (PG) E1, E2, and D2 all stimulated the glucose production by parenchymal liver cells, PGD2 being the most potent. Kupffer and endothelial liver cell media as well as prostaglandins E1, E2, and D2 stimulated the activity of phosphorylase, the regulatory enzyme in glycogenolysis. The data indicate that prostaglandins, present in media from Kupffer and endothelial liver cells, may stimulate glycogenolysis in parenchymal liver cells. This implies that products of Kupffer and endothelial liver cells may play a role in the regulation of glucose homeostasis by the liver.

Alprostadil↗
PubMed1988

Prostaglandin D2 mediates the stimulation of glycogenolysis in the liver by phorbol ester.

The tumour-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), when added to the perfused liver, stimulates glycogenolysis 2-fold. This stimulation is not seen when aspirin is present in the perfusion medium. In isolated parenchymal liver cells. PMA is not able to stimulate glycogenolysis, suggesting that its effect on glycogenolysis might be indirect and depends on the presence of the non-parenchymal liver cell types. To test the possible operation of an indirect mechanism, we measured the amount of prostaglandin (PG) D2 in liver perfusates. After addition of PMA, the amount of PGD2 is doubled, in parallel with the increase in glycogenolysis. Glycogenolysis in both isolated parenchymal liver cells and perfused liver could be stimulated by the addition of PGD2. Our data indicate that stimulation of glycogenolysis in the liver by PMA may be mediated by non-parenchymal liver cells, which produce PGD2 in response to PMA. Subsequently PGD2 activates glycogenolysis in the parenchymal liver cells. The intercellular communication inside the liver in response to PMA adds a new mechanism to the complex regulation of glucose homoeostasis by the liver.

Animals↗
PubMed1988

Reversible inhibition of DNA and protein synthesis by cumene hydroperoxide and 4-hydroxy-nonenal.

To test the possible role of lipid peroxidation in the process of in vitro ageing, human diploid skin fibroblasts were cultured with the lipophilic hydroperoxide cumene hydroperoxide (Chp) or the breakdown product of lipid peroxidation 4-hydroxy-2,3-trans-nonenal (HNE). Both compounds inhibited cellular DNA and protein synthesis in a dose-dependent way. Cells exposed to Chp or to HNE during growth inhibition recovered DNA and protein synthesis within 24 h upon removal of Chp or HNE from the culture medium. Continuously proliferating cells showed only a partial recovery of DNA and protein synthesis. Pre-culturing cells with the lipophilic free radical scavenger vitamin E did not abolish the effect of Chp upon DNA synthesis. Cellular levels of reduced glutathione (GSH) rose slightly during 1 week of culture with HNE, but remained unaltered with Chp. Neither ATP levels nor cellular energy charges were affected during culture with Chp or HNE. So, DNA synthesis is not impaired due to a shortage of nucleotides nor does GSH protect DNA synthesis against the effects of Chp or HNE. These results suggest that oxygen free-radical induced lipid peroxidation is not the cause of the irreversible loss of proliferation occurring during in vitro ageing.

Aging↗
PubMed1988

Superoxide dependent iron release from ferritin in inflammatory diseases.

Convincing evidence is presented that oxygen free radicals are involved in the pathogenesis of rheumatoid arthritis (RA). Superoxide is produced by polymorphonuclear leucocytes (PMN) in synovial fluid and by macrophages in the synovial membrane. Tissue damage typical for free radical attack is detected in RA. No absolute deficiency of protective factors is found in RA compared to controls, but the available protection is insufficient to cope with all radicals formed. The toxicity of superoxide is increased by iron. It is doubtful whether a low molecular weight iron pool is present. Superoxide is able to release iron from ferritin, providing a suitable source of iron, for the formation of hydroxyl radicals. This new pathogenetic mechanism stimulates to the application of iron chelators in the treatment of RA. Preliminary results with desferrioxamine were disappointing because of serious side-effects. Hopefully in the future intra-articular injection of iron chelators with better pharmacodynamics will be possible. The interaction of free radicals and ferritin is probably also involved in the pathogenesis of other inflammatory diseases such as systemic lupus erythematosus, hepatitis, and haemochromatosus.

Animals↗
PubMed1988

Lipid peroxidation in normoxic and ischaemic-reperfused hearts of fish oil and lard fat fed pigs.

The in situ and in vitro rate of lipid peroxidation of hearts were determined in two groups of pigs which had been fed diets which differed only in fatty acid composition for 8 weeks. During the dietary period venous plasma levels of malondialdehyde and lipofuscin were not higher in pigs receiving the highly unsaturated fatty acid-containing mackerel oil than those receiving lard fat. Malondialdehyde was produced in the coronary system of the mackerel oil fed animals. After the heart was subjected to a sequence of short periods of ischaemia (5 min) and reperfusion (10 min), myocardial malondialdehyde production in the mackerel oil fed pigs did not increase. Contribution of prostaglandin synthesis products to myocardial malondialdehyde formation is probably of minor importance. Recovery of regional heart function after the ischaemic periods was similar for both dietary groups. In the phospholipids of sarcolemmal preparations isolated from the left ventricle of mackerel oil fed animals 18:2 n-6 and 20:4 n-6 were partially replaced by 20:5 n-3 and 22:6 n-3. Ischaemia-reperfusion did not alter sarcolemmal fatty acid composition and Ca2+ pumping ATPase activity. Sarcolemmal membrane from mackerel oil fed pigs exposed in vitro to a free radical generating system showed a higher malondialdehyde production than that from lard fat fed pigs. Thus, in spite of the increased susceptibility of heart membranes to free radical generated peroxidation in mackerel oil fed animals, recovery of left ventricular function was similar following multiple short-term periods of ischaemia.

Animals↗
PubMed1988

Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine.

To investigate whether iron is involved in the reperfusion syndrome by aggravating free radical injury, the hearts from iron-loaded and control rats were perfused under normoxic, anoxic, and reperfusion conditions. Normoxic perfusion revealed no change in coronary flow, contractility, or lactate dehydrogenase (LDH) release between these two groups. Under anoxic and reperfusion conditions, however, we found a significant increase of ventricle fibrillation (56% vs. 0%, p less than 0.01, n = 9), a significantly lower recovery of contractility (21 +/- 7.4% vs. 81 +/- 6.6%, mean +/- SEM; p less than 0.001), and a significant increase of LDH release (667 +/- 142 vs. 268 +/- 37 mU LDH/min/g wet wt, mean +/- SEM; p less than 0.05). Administration of either 20 microM of the antioxidant (+)-cyanidanol-3 or 50 microM of the iron-chelator deferoxamine totally prevented the generation of ventricle fibrillation and normalized contractility to control levels in the iron-loaded group. Moreover, 20 microM (+)-cyanidanol-3 significantly lowered LDH release in this period (312 +/- 67 mU), whereas deferoxamine had no protective effect on this LDH release (1,494 +/- 288 mU). Normal hearts appeared to be protected by 20 microM (+)-cyanidanol-3 as well. In this group (n = 6), a significantly higher recovery of contractility (97.1 +/- 3.2% vs. 81 +/- 6.6%, p less than 0.05) and a significantly lower release of LDH (110 +/- 27 vs. 268 +/- 37 mU, p less than 0.05) was found compared with the control group (n = 9). No difference in superoxide dismutase or glutathione peroxidase activity was found between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Covalent cross-links in oxygen free radical altered human immunoglobulin G.

The damaging effect of an oxygen free radical generating system, i.e. ultraviolet irradiation, on human immunoglobulin G (IgG) was studied. The free radical altered IgG was analysed by a high performance liquid chromatograph equipped with a TSK G 3000 SW-column. Gel filtration of 120 min UV-irradiated IgG resulted in three clearly distinguished peaks corresponding to polymer IgG (MW greater than 500 kD), dimer IgG (MW 300 kD) and monomer IgG (MW 150 kD). Analysis of oxygen free radical altered and aggregated IgG by SDS-PAGE and subsequent silver-staining revealed inter- and intra-molecular reduction (by beta-mercaptoethanol)-resistant cross-links between IgG-molecules were formed. Comparison of amino acid analyses of native IgG with oxygen free radical aggregated polymer IgG showed significant reductions in tyrosine- (7.0%) and histidine- (6.5%) content. These findings suggest that tyrosine and histidine are involved in covalent cross-linking between IgG-molecules caused by oxygen free radicals. These alterations on IgG induced by free radical-activity might render it antigenic, and could initiate the production of rheumatoid factors (RF).

Amino Acids↗
PubMed1987

The influence of the chain length of aldehydes on the fluorescence of chromolipids.

Incubation of phosphatidylethanolamine containing liposomes with malondialdehyde and other aldehydes with different chain lengths results in the fluorescence of chromolipids. Relative to malondialdehyde, the fluorescence was greatly enhanced with increasing chain length upon incubation of 2-alkenals with phospholipids. Similar results were found using the total lipid extracted from erythrocyte ghosts. It seems that the hydrophobic character of the aldehydes is important for the amount of fluorescence detected in lipid bilayers.

Aldehydes↗
PubMed1987

Human serum sialo transferrins in diseases.

Using isoelectric focusing and crossed immunoelectrophoresis on ready-made Immobiline Dry Plates, pH 5-6, we were able to separate human serum transferrin in subfractions with different sialo acid content. The amount of these subfractions is significant different in sera of patients with diseases like CA, RA, haemochromatosis and in sera of pregnant women.

Female↗
PubMed1987

Influence of cumene hydroperoxide and 4-hydroxynonenal on the glutathione metabolism during in vitro ageing of human skin fibroblasts.

Cumene hydroperoxide (Chp) and 4-hydroxynonenal (HNE) were used to investigate the effect of peroxidative challenge upon the glutathione (GSH) metabolism of human skin fibroblasts. Cellular GSH contents decreased during short-term incubations with Chp and oxidised glutathione (GSSG) was formed concomitantly. During longer incubations the GSH level was restored and the substrate flux through the pentose phosphate shunt increased. So in the presence of hydroperoxides the GSH level is maintained by reduction of GSSG. HNE caused a strong decrease in cellular GSH contents. Prolonged incubation with HNE lead to a rise in GSH contents above the basal level. The flux through the pentose phosphate shunt did not change during exposure to HNE. Hence, during incubation with HNE the cell maintains its GSH content by de novo synthesis of GSH. This conclusion is further substantiated by the findings with a cell strain deficient in GSH synthetase. These cells survived if incubated with Chp but not if exposed to HNE. GSH contents of normal cells from phase II (young) cultures and from phase III (aged) cultures responded similarly to Chp during short-term incubations and during a week of culture with the test compound. The flux through the pentose phosphate shunt rose much more in phase III than in phase II cells when incubated with the same concentration series of Chp. We conclude that during in vitro ageing the amount of NADPH needed to maintain cellular GSH levels in the presence of hydroperoxides increases, while the capacity to respond to such a challenge is not affected.

Adult↗
PubMed1987

Lipid peroxidation and myocardial ischaemic damage: cause or consequence?

Compelling evidence has been accumulated which indicates that myocardial tissue damage occurring during reperfusion after an ischaemic period may partly be due to the formation of oxygen free radicals and subsequent peroxidative processes. It has been well established that the actual toxicity of free radicals is dependent on the presence of free iron in the heart tissue. Based upon the hypothesis of McCord et al., proposing xanthine oxidase mediated formation of superoxide (O2-.) during the conversion of ATP-breakdown product(s) (hypo)xanthine to urate, we studied whether xanthine oxidase was able to mobilize free iron from the intra- and extracellular iron-binding proteins, ferritin and transferrin. It appeared that there was an O2-.-dependent and O2-.-independent mechanism by which xanthine oxidase could mobilize iron from ferritin while no iron mobilization from transferrin was detectable. The capacity of xanthine oxidase to mobilize iron from ferritin by an O2-.-independent mechanism implies that already during the anoxic/ischaemic period, iron may become available in the tissue which, upon the re-entrance of O2, catalyzes the formation of the very reactive OH radicals. The interaction between endothelial cells and cardiocytes in free radical homeostasis is discussed with the emphasis on the tissue localization of xanthine oxidase. The latter is located in endothelial cells implying an interaction between xanthine oxidase-induced endothelial cells initiated lipid peroxidation and the actual overall myocardial tissue damage.

Animals↗