{"title":"Characterization of an inositol 1,3,4,5-tetrakisphosphate 3-phosphatase from porcine brain.","authors":"A Höer, E Oberdisse","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Some of the properties of a high affinity Ins(1,3,4,5)P4 3-phosphatase (Km approximately 400 nM) from the soluble fraction of pig brain are presented. Several inositol polyphosphates reduced the activity of the Ins-(1,3,4,5)P4 3-phosphatase. The most effective inhibitors were Ins(1,3,4, 5,6)P5 and InsP6 with Ki-values of about 60 nM and 3 nM, respectively. We could show that at least InsP6 is a likely substrate of the Ins(1,3,4,5)P4 3-phosphatase, which degraded InsP6 with a very low reaction velocity. This 3-phosphatase may be important for the metabolism of higher phos-phorylated inositol polyphosphates.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S16-8"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12507503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mouse peritoneal macrophages contain an acylating system specific for twenty-carbon polyunsaturated fatty acids. A study with intact cells.","authors":"B Fernández, J A Solís-Herruzo, J Balsinde","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>It is widely recognized that in addition to regulating the expression and activity of arachidonic acid (AA)-metabolizing enzymes, the availability of free AA limits eicosanoid biosynthesis. AA participates in a deacylation/reacylation cycle of membrane phospholipids in which the fatty acid is cleaved by phospholipase A2 and reesterified by acyltransferase. Thus, free AA can become available either by phospholipase A2 activation or by inhibition of fatty acid reincorporation. We observed that exposure of [3H]AA-prelabeled macrophages to micromolar concentrations of unlabeled AA resulted in a net release of 3H-radioactivity into the extracellular medium. This was not the consequence of phospholipase A2 activation, but of impaired reesterification of previously liberated [3H]AA. The eicosanoid precursors eicosatrienoic acid (ETA) and eicosapentaenoic acid (EPA) mimicked the effect of unlabeled AA on 3H-radioactivity release from [3H]AA-prelabeled macrophages, but all other fatty acids tested were ineffective. Similarly, only AA, ETA and EPA were able to inhibit [3H]AA uptake by macrophages, all other fatty acids being ineffective. From these data, it is concluded that intact macrophages contain an acylating system specific for the eicosanoid precursors AA, ETA and EPA. Altogether, the results of this study underscore the importance of fatty acid reacylation in controlling free AA levels in macrophages.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 2","pages":"115-20"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of calcimycin-induced stimulation of cytosolic calcium in human PMN by a LTB4 receptor antagonist.","authors":"R Heckenberger, K Schrör","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study investigates the significance of PMN-derived LTB4 for PMN activation by using a selective LTB4 antagonist (SC 41930). Human PMN were stimulated by platelet-activating-factor (PAF, 3 microM), a receptor dependent agonist, or by calcimycin (A 23187, 10 microM), a receptor independent agonist. PMN activation was determined by LTB4 release and changes in free cytosolic Ca++ levels. Pretreatment of the PMN with SC 41930 (0.1-10 microM) caused a concentration-dependent inhibition of agonist induced rise in cytosolic Ca++ with both PAF and calcimycin. Interestingly, at the same concentrations of SC 41.930, there was a concentration-dependent inhibition of LTB4 release. Control experiments with a cell-free 5-lipoxygenase preparation did not show any direct effect of SC 41930 on the enzyme under conditions when nordihydroguiaretic acid was active. The data demonstrate a nonselective inhibition of agonist induced PMN activation by the LTB4 receptor antagonist SC 41930 and suggest that formation of endogenous LTB4 is involved in a positive feed-back loop that is required for maximum stimulation of PMN function even by a calcium ionophore.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S23-5"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12507504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of 25-hydroxycholesterol on cytotoxicity and prostacyclin production in cultured human umbilical arterial endothelial cells.","authors":"K Kawamura, F A Kummerow","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of cholesterol or 25-hydroxycholesterol on DNA synthesis and prostacyclin synthesis by cultured human umbilical arterial endothelial cells was investigated. Cells incubated with 25-hydroxycholesterol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and increased prostacyclin production as compared to either the control or the pure cholesterol group. 25-hydroxycholesterol caused a concentration- and time-dependent increase in prostacyclin synthesis. The intracellular free calcium concentration of endothelial cells incubated with 25-hydroxycholesterol was markedly increased in a time-dependent manner. Calcium uptake by endothelial cells incubated with 25-hydroxycholesterol for 24 h was markedly increased. It is suggested that 25-hydroxycholesterol may depress DNA synthesis and increase prostacyclin synthesis via an elevation in the intracellular free calcium concentration of endothelial cells.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 1","pages":"29-34"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12589784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thromboxane as diagnostic tool and therapeutic target in cardiovascular disease.","authors":"R Lorenz, P C Weber","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Our studies were first directed to improvements in analytical methodology of thromboxane metabolism in man. These methods were then applied in a variety of clinical settings to better define the clinical spectrum and timecourse of platelet related pathomechanisms. They were also applied in studies aiming at optimized therapeutic interventions. Such biochemical guidelines are essential for the optimal planning of future clinical studies.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S53-5"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12620250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sulotroban selectively inhibits thromboxane-receptor-mediated responses in the peripheral vascular bed of the cat.","authors":"P Kvamme, R K Minkes, P J Kadowitz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of Sulotroban (BM 13.177, SK&F 95587) were investigated under conditions of controlled blood flow in the hindquarters and mesenteric vascular beds of the cat. Injections of the thromboxane (TX) A2 mimics, U46619 and U44069, caused dose-related increases in perfusion pressure. After administration of SK&F 95587, vasoconstrictor responses to the TXA2 mimics were reduced significantly, and the dose-response curves were shifted to the right in a parallel fashion. Responses to norepinephrine, phenylephrine, tyramine, endothelin-1, angiotensin II, BAY K8644, acetylcholine, sodium nitroprusside, isoproterenol, lemakalim, prostaglandin (PG) E1, and PGF2 alpha, agents which alter vascular resistance by a variety of mechanisms, were not changed by the TXA2 receptor antagonist. However, SK&F 95587 reduced mesenteric vasoconstrictor responses to PGD2. Results of the present study indicate that SK&F 95587 blocks TX-receptor-mediated responses in the hindquarters circulation of the cat in a competitive and selective manner and reduces mesenteric vascular responses to the TXA2 mimics, as well as PGD2. These data suggest that this antagonist would be useful in studies on the role of TXA2 in physiologic and pathophysiologic processes in the systemic vascular bed of the cat.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 3-4","pages":"127-33"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12466825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B Rabinowitz, M Arad, E Elazar, R Klein, Y Har Zahav
{"title":"Epicardial versus endocardial \"in mirror\" changes in prostaglandin synthesis after short periods of ischemia and reperfusion.","authors":"B Rabinowitz, M Arad, E Elazar, R Klein, Y Har Zahav","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cardiac ischemia and reperfusion are associated with increased prostaglandin levels in the coronary venous effluent. This study implemented an in vivo-in vitro technique to investigate regional alterations in heart tissue PGE2 and PGF2 alpha de novo production. Canine endocardial and epicardial explants were incubated following 5 min regional ischemia, or 5 min ischemia with 10 min reperfusion, induced in vivo in two groups of animals (n = 10 and 6, respectively). Ischemia produced a significant upsurge in endocardial but not in epicardial prostaglandin synthesis as compared with the non-ischemic zone: 7.6 +/- 0.7 versus 4.5 +/- 0.5 pg/mg tissue per h in PGE2 (P < 0.001) and 8.8 +/- 1.2 versus 6.8 +/- 1.2 pg/mg per h PGF2 alpha (P < 0.01). Following reperfusion, PGE2 was higher in the apparently normal than in the affected endocardium (5.8 +/- 0.6 versus 4.4 +/- 0.5 pg/mg per h, P < 0.05). Opposite changes occurred in the reperfused epicardium: 8.2 + 0.9 versus 4.9 +/- 0.7 pg/mg per h PGE2 (P < 0.01) and 11.1 +/- 0.9 versus 6.0 +/- 0.6 pg/mg per h PGF2 alpha (P < 0.001), for the reperfused as compared to the \"normal\" region, respectively. Our findings imply that the left ventricular wall is not homogeneous in its eicosanoid response to ischemia and reperfusion. \"In mirror\" changes were found between endocardium end epicardium and between the injured and the apparently normal regions.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 3-4","pages":"163-7"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12467465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
W Engels, P J Lemmens, A D Muller, M C Van Dam-Mieras, G Hornstra
{"title":"The effect of viral infection on eicosanoid formation and procoagulant activity of rat peritoneal macrophages. Role of the dietary fat type.","authors":"W Engels, P J Lemmens, A D Muller, M C Van Dam-Mieras, G Hornstra","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of dietary manipulation on eicosanoid formation in rat peritoneal macrophages was studied in relation to some of their effector functions: cellular procoagulant activity, production of reactive oxygen species (measured as chemiluminescence), and phagocytosis of antibody-coated erythrocytes. Rats were fed adequate diets for eight weeks containing mackerel oil (MO), sunflowerseed oil (SO) or hydrogenated coconut oil (HCO). The release of eicosanoids from resident macrophages stimulated by opsonized zymosan was significantly lower for the MO group as compared to the other dietary groups. Infection of the animals via intraperitoneal injection with rat cytomegalovirus resulted in a significant decrease in eicosanoid production in all groups, irrespective of dietary fat type. However, in the HCO group a partial restoration of TXB2 and HHT production could be observed at day 10 post infection. Resident macrophages obtained from the mackerel oil fed animals showed a significantly higher procoagulant activity than those from the other diet groups. Infection of the animals resulted in an increase in procoagulant activity in all groups. In contrast, no significant differences in chemiluminescence and in phagocytosis were detected between macrophages obtained from rats fed the different diet groups. It is concluded that peritoneal macrophages obtained from mackerel oil fed rats produce less eicosanoids and are more procoagulant than those from the other dietary groups, but a viral infection eradicates these differences. Therefore, a correlation between eicosanoid formation and effector functions studied could not be established.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 2","pages":"73-80"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12507501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prostaglandin 9-ketoreductase from pig and human kidney: purification, properties and identity with human carbonyl reductase.","authors":"A Schieber, S Ghisla","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostaglandin 9-ketoreductase has been purified to apparent homogeneity from pig and human kidney with an overall yield of 6%. The enzyme has a molecular mass of 34 kDa, it is present as an active monomer in diluted solution and contains approx. 2 equivalents Zn++/mole enzyme. It is stereoselective for the pro(S) hydrogen of NADPH and reduces the prostaglandin 9-keto group to yield 90% prostaglandin F2 alpha and 8% of the beta-form. An extensive study of the catalytic properties was carried out, which leads to the conclusion that the enzyme function in vivo is unlikely a catalysis of oxidation/reduction at the prostaglandin 9-position. Five peptides from the pig kidney enzyme were sequenced and compared with the sequence of carbonyl reductase from human placenta. The identity is > 90% and this, together with the immunological cross-reactivity with human brain carbonyl reductase, most strongly suggests that prostaglandin 9-ketoreductase and carbonyl reductase are the same enzyme.</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S37-8"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12619693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Priming mechanisms and induction of heat shock proteins in human polymorphonuclear granulocytes induced by eicosanoids and cytokines.","authors":"W König, M Köller, J Brom","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Priming of human polymorphonuclear granulocytes (PMNs) with cytokines (IL-3, IL-6, TNF-alpha) followed by a subsequent stimulation (FMLP) led to an enhanced polymerization of actin and GTPase-activity which correlated to a loss of ras immunoreactivity and an increased expression of Rab proteins. Furthermore TNF-alpha and 12-HETE induced the heat shock proteins (hsp 70 family) in PMNs as was demonstrated by metabolic radiolabeling and Western blotting (anti-hsp 72). This activation of the stress response exerted a protective function towards a subsequent lytic attack by a bacterial cytolysin (leukocidin).</p>","PeriodicalId":11520,"journal":{"name":"Eicosanoids","volume":"5 Suppl ","pages":"S39-41"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12619694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}