共查询到20条相似文献,搜索用时 15 毫秒
1.
We have examined the role of phospholipid-sensitive calcium-dependent protein kinase (protein kinase C) in prostaglandin E2 synthesis by monolayer cultures of swine granulosa cells. Specific phorbol ester derivatives known to activate protein kinase C significantly augmented the production of prostaglandin E2. These stimulatory actions were dose and time-dependent, and could be abolished by the cyclooxygenase inhibitor, indomethacin, or the protein synthesis inhibitor, cycloheximide. Moreover, the rank order of potency of phorbol esters in enhancing prostaglandin E2 production was concordant with that demonstrated for activation of protein kinase C. Phorbol ester in conjunction with the divalent cation ionophore, A23187, increased prostaglandin E2 production synergistically. In addition, a non-phorbol stimulator of protein kinase C, 1-octanoyl-2-acetylglycerol, also significantly enhanced prostaglandin E2 biosynthesis. The stimulated synthesis of prostaglandin E2 was confirmed by high-pressure liquid chromatographic purification of this radiolabeled metabolite of 3H-arachidonic acid, and by capillary gas chromatography high-resolution mass spectrometry. Thus, the present studies indicate that the protein kinase C effector pathway is functionally coupled to prostaglandin E2 production in the swine granulosa cell. 相似文献
2.
Prostaglandin E1 and prostaglandin E2 speed up the dark-induced (scotonastic) and light-induced (photonastic) leaflet movements of Cassia fasciculata. The precursors of prostaglandin biosynthesis, homo -linolenic and arachidonic acids, and an intermediary product, prostaglandin-interm-5, act in the same manner on these movements. Inhibitors of prostaglandin biosynthesis, indomethacin and phenylbutazone, inhibited the scotonastic but promoted the photonastic movements in an unexpected way. Since the pulvinar movements are mediated by water and ion migrations, the observed modifications of these movements indicate that prostaglandins and their precursors may affect, as in animal cells, processes linked to a variation of membrane permeability.Abbreviations PGE1
prostaglandin E1
- PGE2
prostaglandin E2 相似文献
3.
C.R. Pace-Asciak 《Prostaglandins & other lipid mediators》1977,13(4):649-660
The prostaglandin biosynthetic and catabolic capacity of homogenates of lungs fetal sheep of various gestational ages was measured. Prostaglandin biosynthesis was assayed by the deuterium-isotope dilution technique making us e of mas fragmentography whereas prostaglandin catabolism was measured by the radioisotope-dilution method described previously (Pace-Asciak, C.R. and Rangaraj, G. (1976) J. Biol. Chem. 251, 3381–3385).Homogenates of lung sform fetuses of all ages tested (40 days to term) formed both prostaglandins E2 and F2α; although prostaglandin F2α was formed to a greater extent than prostaglandin E2 by the 40 day lung, prostaglandin E2 increased with increasing age until at term the ratio of both prostaglandins approached unity. Total prostaglandin biosynthesis (E2 + F2α) rose gradually with age (approx. 3 fold increase between 40 days and term). Prostaglandin F2α catabolism occurred mainly by the prostaglandin 15-hydroxy dehydrogenase pathway; this activity was detectable even at 40 days and remained unchanged up to 80 days. Prostaglandin catabolic activity rose sharply at 90 days (approx. 3 fold) with a maximum around 110 days (approx. 4 fold) decreasing back to 40 day levels by term (143 days).The increasing prostaglandin catabolic activity around 90–100 days in this species is discussed in relation to the hemodynamic changes in the lungs starting around this age and the appearance of surfactant. Prostaglandin catabolism might play an important role in the developing organ controlling steady state concentrations of prostaglandins during certain periods of organogenesis. 相似文献
4.
M.Linette Casey Paul C. MacDonald Murray D. Mitchell 《Prostaglandins & other lipid mediators》1984,27(3):421-427
In the present investigation, we found that among the prostanoids that human amnion cells, which are maintained in monolayer culture, secrete into the culture medium, prostaglandin E2 is by far the predominant one. In the presence of inhibitors of prostaglandin synthase, the production of prostaglandin E2 by these cells is abolished. Amnion cells maintained in the presence of fetal calf serum produce greater quantities of prostaglandin E2 than do cells maintained in serumless medium. In the amnion cells, there is little or no metabolism of prostaglandin E2; this also is true of amnion tissue. The unique characteristics of prostaglandin biosynthesis and metabolism by human amnion cells in monolayer culture are identical with those of human amnion tissue. Hence, we suggest that amnion cells in culture constitute an excellent model for investigations of the regulation of prostaglandin E2 biosynthesis in this tissue. 相似文献
5.
Zahir Qureshi Lauren M. Cagen 《Biochemical and biophysical research communications》1982,104(4):1255-1263
Slices of rabbit renal medulla and rabbit renal papilla were incubated with a mixture of [1-14C]-arachidonic acid and [5,6,8,9,11,12,14,15-3H]-arachidonic acid. In both tissues, comparison of the isotope ratios of the radioactive products with the isotope ratio of the added arachidonic indicated that: (a) there was no discernable isotope effect in the biosynthesis of prostaglandin E2; (b) prostaglandin F2α was formed by reduction of prostaglandin H2 and not by reduction of prostaglandin E2; and (c) most of the radioactive product arose from arachidonic acid that had been incorporated into the tissue and not from the direct action of cyclooxygenase on arachidonic acid in the medium. 相似文献
6.
KEITH CROWSHAW 《Nature: New biology》1971,231(25):240-242
THIS report describes the biosynthesis of the naturally occurring renal prostaglandins E2 (PGE2) and F2α (PGF2α)1,2 by homogenates and slices of rabbit renal medulla, from endogenous precursors. I have confirmed that rabbit renal cortex contains little prostaglandin and cannot synthesize them from endogenous lipids3. Hamberg has reported that arachidonic acid, which is converted to PGE2 and PGF2α by enzymes present in ram seminal vesicles4, can be efficiently converted to PGE2 and PGF2α by homogenates of rabbit renal medulla3. I have now confirmed that arachidonic acid, added to such medullary homogenates, can increase the quantities of prostaglandins synthesized. There was no evidence that the major prostaglandin biosynthesized, PGE2, was further metabolized to inactive products. 相似文献
7.
The present study has been performed to investigate how PGs would participate the hatching process. Effects of indomethacin, an antagonist to PGs biosynthesis, on the hatching of mouse blastocysts were examined in vitro. Furthermore, it was studied that prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) or 6-keto-prostaglandin F1α (6-keto-PGF1α) were added to the culture media with indomethacin. (1) The hatching was inhibited by indomethacin yet the inhibition was reversible. (2) In the groups with indomethacin and PGE2, no improvement was seen in the inhibition of hatching and the inhibition was irreversible. (3) In the groups with indomethacin and PGF2α, inhibition of hatching was improved in comparison with the group with indomethacin. (4) In the groups with indomethacin and 6-keto-PGF1α, no improvement was seen. The above results indicated that PGF2α possibly had an accelerating effect on hatching and a high concentration of PGE2 would exert cytotoxic effect on blastocysts. 相似文献
8.
Gerhard Fürstenberger Friedrich Marks 《Biochemical and biophysical research communications》1978,84(4):1103-1111
The proliferative response of mouse epidermis to the phorbolester TPA (10 nmoles) in vivo is completely inhibited by a single topical application of indomethacin one hour before TPA. DNA labeling in normal mouse epidermis is not significantly depressed by the drug. The inhibition can be reversed by applying prostaglandin E2 (>3 nmoles) simultaneously with TPA, whereas prostaglandin F2α (100 nmoles) is ineffective. The indomethacin-sensitive event is restricted to the first hour after phorbol ester treatment. TPA-induced skin inflammation is not influenced by the drug. It is proposed that prostaglandin E2, or a closely related compound, mediates the mitogenic effect of TPA in mouse skin. 相似文献
9.
Anshumali Chaudhari Michael A. Kirschenbaum 《Prostaglandins & other lipid mediators》1983,26(5):689-699
We have previously demonstrated that decreased cortical prostaglandin metabolism can contribute significantly to an increase in renal tissue levels and activity of prostaglandin E2 in bilateral ureteral obstruction, a model of acute renal failure. In the present study, we have further investigated whether alterations in prostaglandin metabolism can occur in a nephrotoxic model of acute renal failure. Prostaglandin synthesis, prostaglandin E2 metabolism (measured as both prostaglandin E2-9-ketoreductase and prostaglandin E2-15-hydroxydehydrogenase activity), and tissue concentration of prostaglandin E2 were determined in rabbit kidneys following an intravenous administration of uranyl nitrate (5 mg/kg). No changes in the rates of cortical microsomal prostaglandin E2 and prostaglandin F2α synthesis were noted at the end of 1 and 3 days, while medullary synthesis of prostaglandin E2 fell by 47% after 1 day and 43% after 3 days. Cortical cytosolic prostaglandin E2-9-ketoreductase activity was found to be decreased by 36% and 76% after 1 and 3 days respectively. No significant changes were noted in cortical cytosolic prostaglandin E2-15-hydroxydehydrogenase activity after 3 days. Cortical tissue levels of prostaglandin E2 increased by 500% at the end of 3 days. These data demonstrate that in nephrotoxic acute renal failure, decreased prostaglandin metabolism (i.e., prostaglandin E2-9-ketoreductase activity) can result in increased tissue levels of prostaglandin E2 in the absence of increased prostaglandin synthesis and suggest that alterations in prostaglandin metabolism may be an important regulator of prostaglandin activity in acute renal failure. 相似文献
10.
11.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostanoid formation and represent prevalent therapeutics for treatment of inflammatory disorders. However, NSAIDs are afflicted with severe side effects, which might be circumvented by more selective suppression of pro-inflammatory eicosanoid biosynthesis. This concept led to dual inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase that are crucial enzymes in the biosynthesis of pro-inflammatory prostaglandin E2 and leukotrienes. The potential of their dual inhibition in light of superior efficacy and safety is discussed. Focus is placed on natural products, for which direct inhibition of mPGES-1 and leukotriene biosynthesis has been confirmed. 相似文献
12.
The effects of several co-factors and bivalent cations on the activity of prostaglandin synthetase isolated from goat seminal
vesicles were studied. Ca2+ appears to play a regulatory role in the biosynthesis of prostaglandin E2 by goat vesicular microsomes as the normal parabolic time course of synthesis changed to a sigmoid curve in the presence
of 4 mM Ca2+ and to nearly a hyperbolic pattern when the microsomes were preincubated with the metal ions. The Ca2+ modulated reaction showed increased rate of prostaglandin E2 synthesis only when the period of incubation was extended beyond 30 min. The co-factor requirement of the goat enzyme was
similar to that of the bovine and ovine prostaglandin synthetase systems. 相似文献
13.
L.C. Best M.B. McGuire T.J. Martin F.E. Preston R.G.G. Russell 《Biochimica et Biophysica Acta (BBA)/General Subjects》1979,583(3):344-351
The effects on human platelets of two synthetic analogues of prostaglandin endoperoxides were examined in order to explore the relationship between aggregation and prostaglandin and cyclic nucleotide metabolism, and to help elucidate the role of the natural endoperoxide intermediates in regulating platelet function.Both analogues (Compound I, (15S)-hydroxy-9α,11α-(epoxymethano)-prosta-(5Z,13E)-dienoic acid, and Compound II, (15S)-hydroxy-11α,9α-(epoxymethano)-prosta-(5Z,13E)-dienoic acid) caused platelets to aggregate, an effect which could be inhibited by prostaglandin E1 but not by indomethacin. Compound II produced primary, reversible aggregation at concentrations which did not induce release of 5-hydroxytryptamine. Production of thromboxane B2 and malonyldialdehyde was monitored as an index of endogenous production of prostaglandin endoperoxides and thromboxane A2 and were increased after incubation of human platelets with thrombin, collagen or arachidonic acid. However, neither malonydialdehyde nor thromboxane B2 levels were significantly influenced by the endoperoxide analogues. Both analogues produced a small elevation of adenylate cyclase activity in platelet membranes and of cyclic AMP content in intact platelets, but neither had any modifying effect on the much greater stimulation of adenylate cyclase and cyclic AMP levels by prostaglandin E1. Of all the aggregating agents tested, only arachidonic acid produced any significant increase in platelet cyclic GMP levels.These results suggest that the epoxymethano analogues of prostaglandin endoperoxides induce platelet aggregation independently of thromboxane biosynthesis and without inhibiting adenylate cyclase or lowerin platelet cyclic AMP levels. They therefore differ from better known aggregating agents such as ADP, epinephrine and collagen, which increase thromboxane A2 production and reduce cyclic AMP levels, at least in platelets previously exposed to prostaglandin E1. 相似文献
14.
Using 2-amino-6-(5'-2'-deoxyphosphoribosyl)-amino-5- or -6-formamido-6-hydroxypyrimidine (dFPyd-P3), a specific inhibitor of tetrahydrobiopterin (BH4) synthesis, cerebral pools of BH4 were reduced to half of that of controls; while, simultaneously, the biosynthesis of L-erythrodihydroniopterin (BH2) from GTP was inhibited by about 98%. Nevertheless, there was no effect on the cerebral levels of serotonin, dopamine, norepinephrine or on the biosynthesis of prostaglandin E2 or F1. The data are presented in evidence that the absolute level of the cofactor (BH4) is not regulatory of amine or protaglandin biosynthesis . Amine and prostaglandin biosynthesis proceeded even at cofactor concentrations of 9×107 M nsuggesting that their biosynthesis is dependent on the rate of H+ + e shuttle between BH2 and BH4. 相似文献
15.
Enzymic coupling of acylhydrolase and prostaglandin synthase activities in subcellular fractions from rabbit renal medulla
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We have recently shown that mitochondrial and plasma-membrane fractions from kidney medulla possess Ca2+-stimulated acylhydrolase and prostaglandin synthase activities. The nature of the enzymic coupling between the Ca2+-stimulated arachidonic acid release and its subsequent conversion into prostaglandins was investigated in subcellular fractions from rabbit kidney medulla. Plasma-membrane, mitochondrial and microsomal fractions were found to have similar apparent Km values for conversion of added exogenous arachidonate into prostaglandins. The rate of prostaglandin biosynthesis (Vmax.) from added arachidonic acid in the microsomal fraction was approx. 2-fold higher than in the other subcellular fractions. In contrast, prostaglandin E2 synthesis from endogenous arachidonate in plasma-membrane and mitochondrial fractions was 3–4-fold higher than in microsomes. Furthermore, Ca2+ stimulated endogenous arachidonate deacylation and prostaglandin E2 generation in the former two fractions but not in microsomes. In mitochondrial or crude plasma-membrane fractions, in which prostaglandin biosynthesis was inhibited with aspirin, arachidonate released from these fractions was converted into prostaglandins by the microsomal prostaglandin synthase. Thus an intracellular prostaglandin generation process that involves inter-fraction transfer of arachidonic acid can operate. Prostaglandin generation by such an inter-fraction process is, however, less efficient than by an intra-fraction process, where arachidonic acid released by mitochondria or crude plasma membranes is converted into prostaglandins by prostaglandin synthase present in the same fraction. This demonstrates the presence of a tight intra-fraction enzymic coupling between Ca2+-stimulated acylhydrolase and prostaglandin synthase enzyme systems in both mitochondrial and plasma-membrane fractions. 相似文献
16.
17.
The release of prostaglandin E2 and F2α, thromboxane B2 and 6-keto-prostaglandin F1α was measured in isolated human placental cotyledons perfused under high- and low-oxygen conditions. Also the effect of reoxygenation on prostaglandin production was studied. During the high-oxygen period, prostaglandin E2 accounted for 44 % and 6-keto-prostaglandin F1α for 28 % of all prostaglandin release, and the rank order of prostaglandin release was E2 > 6-keto-prostaglandin F1α > thromboxane B2 > prostaglandin F2α. Hypoxia had no significant effect on quantitative prostaglandin release, but the ration of prostaglandin E2 to prostaglandin F2α was significantly increased. After the hypoxic period during reoxygenation the release of 6-keto-prostaglandin F1α was significantly decreased, as was the ratio of 6-keto-prostaglandin F1α to thromboxane B2. Also the ratio of the vasodilating prostaglandins (E2, 6-keto-prostaglandin F1α) to the vasocontricting prostaglandins (thromboxane B2, prostaglandin F2α) was decreased during reoxygenation period. With the constant flow rate, the perfusion pressure increased during hypoxia in six and was unchanged in three preparation. The results indicate that changes in the tissue oxygenation in the placenta affect prostaglandin release in the fetal placental circulation. This may also have circulatory consequences. 相似文献
18.
The role of gibberellin biosynthesis in the control of growth and flowering in Matthiola incana 总被引:1,自引:0,他引:1
Tamotsu Hisamatsu Masaji Koshioka Satoshi Kubota Yukihiro Fujime Rod W. King Lewis N. Mander 《Physiologia plantarum》2000,109(1):97-105
Recently, it was found that stem elongation and flowering of stock Matthiola incana (L.) R. Br. are promoted by exogenous gibberellins (GAs), including GA4, and also by acylcyclohexanedione inhibitors of GA biosynthesis, such as prohexadione‐calcium (PCa) and trinexapac‐ethyl (TNE). Here, because it was unclear how GA biosynthetic inhibitors could promote stem elongation and flowering, their effect on GA biosynthesis has been examined by quantifying endogenous GA levels; also, the sensitivity of stem elongation and flowering to various GAs in combination with the inhibitors was examined. Stem elongation and flowering were most effectively promoted by GA4 when combined with PCa and, next in order, by 2,2‐dimethyl‐GA4, PCa, GA4+TNE, TNE, GA9+PCa and by GA4. There was little or no promotion by GA1, GA3, GA9, GA13, GA20 and 3‐epi‐2,2‐dimethyl‐GA4. Both the promotive effects of the acylcyclohexanediones on stem elongation and flowering, particularly when applied with GA4, and the fact that TNE caused a build‐up of endogenous GA4 imply that one effect of TNE at the lower dose involved an inhibition of 2β‐hydroxylation of GA4 rather than an inhibition of 20‐oxidation and 3β‐hydroxylation of GAs which were precursors of GA4. Overall, these results indicate that: (1) GAs with 3β‐OH and without 13‐OH groups (e.g. GA4) are the most important for stem elongation and flowering in M. incana; (2) growth promotion rather than inhibition can result if an acylcyclohexanedione acts predominantly to slow 2β‐hydroxylation and so slows inactivation of active gibbberellins, including GA4. It follows that a low dose of an acylcyclohexanedione can be a ‘growth enhancer’ for any applied GA that is liable to inactivation by 2β‐hydroxylation. 相似文献
19.
Prostaglandin production by mouse fibrosarcoma cells in culture: inhibition by indomethacin and aspirin 总被引:10,自引:0,他引:10
L Levine P M Hinkle E F Voelkel A H Tashjian 《Biochemical and biophysical research communications》1972,47(4):888-896
Five clonal strains of mouse tumor cells (HSDM1) synthesize and secrete large quantities (0.70-2.0 μg/mg cell protein/24 hr) of prostaglandin E2. Five lines of control cells did not synthesize significant amounts of prostaglandins. HSDM1 cells produce prostaglandin E2 during both the logarithmic and stationary phases of the cell growth cycle. Prostaglandin production was inhibited by aspirin-like drugs; for example, 50% inhibition was obtained with as little as 3 × 10−9 M indomethacin. We conclude that the HSDM1 cell system will serve as a useful model system to study prostaglandin synthesis and secretion. 相似文献
20.
We examined the gibberellin (GA) and ethylene regulation of submergence-induced elongation in seedlings of the submergence-tolerant lowland rice (Oryza sativa L.) cvs Senia and Bomba. Elongation was enhanced after germination to facilitate water escape and reach air. We found that submergence-induced elongation depends on GA because it was counteracted by paclobutrazol (an inhibitor of GA biosynthesis), an effect that was negated by GA3. Moreover, in the cv Senia, submergence increased the content of active GA1 and its immediate precursors (GA53, GA19 and GA20) by enhancing expression of several GA biosynthesis genes (OsGA20ox1 and -2, and OsGA3ox2), but not by decreasing expression of several OsGA2ox (GA inactivating genes). Senia seedlings, in contrast to Bomba seedlings, did not elongate in response to ethylene or 1-aminocyclopropane-1-carboxylic-acid (ACC; an ethylene precursor) application, and submergence-induced elongation was not reduced in the presence of 1-methylcyclopropene (1-MCP; an ethylene perception inhibitor). Ethylene emanation was similar in Senia seedlings grown in air and in submerged-grown seedlings following de-submergence, while it increased in Bomba. The expression of ethylene biosynthesis genes (OsACS1, -2 and -3, and OsACO1) was not affected in Senia, but expression of OsACS5 was rapidly enhanced in Bomba upon submergence. Our results support the conclusion that submergence elongation enhancement of lowland rice is due to alteration of GA metabolism leading to an increase in active GA (GA1) content. Interestingly, in the cv Senia, in contrast to cv Bomba, this was triggered through an ethylene-independent mechanism. 相似文献