scholarly journals Effects of bivalent cations on prostaglandin biosynthesis and phospholipase A2 activation in rabbit kidney medulla slices

1979 ◽  
Vol 182 (3) ◽  
pp. 821-825 ◽  
Author(s):  
A Erman ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Inhibitory Effect ◽  
Rabbit Kidney ◽  
Dependent Manner ◽  
Kidney Medulla ◽  
Bivalent Cations ◽  
Tissue Lipids

The bivalent cations Ca2+, Mg2+, Co2+, Mn2+, Sr2+ and Ba2+ were compared for their stimulatory or inhibitory effect on prostaglandin formation in rabbit kidney medulla slices. Ca2+, Mn2+ and Sr2+ ions stimulated prostaglandin generation up to 3–5-fold in a time- and dose-dependent manner (Ca2+ greater than Mn2+ congruent to Sr2+). The stimulation by Mn2+ (but not by Sr2+) was also observed in incubations of medulla slices in the presence of Ca2+. Mg2+ and Co2+ ions were without significant effects on either basal or Ca2+-stimulated prostaglandin synthesis. The stimulatory effects of Ca2+, Mn2+ and Sr2+ on medullary generation of prostaglandin E2 were found to correlate with their stimulatory effects on the release of arachidonic acid and linoleic acid from tissue lipids. The release of other fatty acids was unaffected, except for a small increase in oleic acid release. As both arachidonic acid and linoleic acid are predominantly found in the 2-position of the glycerol moiety of phospholipids, the stimulation by these cations of prostaglandin E2 formation appears to be mediated via stimulation of phospholipase A2 activity.

scholarly journals Prostaglandin biosynthesis and lipolysis in subcellular fractions from rabbit kidney medulla

1981 ◽  
Vol 194 (3) ◽  
pp. 957-961 ◽  
Author(s):  
A Erman ◽  
A Raz
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Plasma Membranes ◽  
Subcellular Fractions ◽  
Rabbit Kidney ◽  
Concomitant Increase ◽  
Kidney Medulla ◽  
Prostaglandin Biosynthesis

Three separate prostaglandin-generating activities are associated with plasma membranes, mitochondria and microsomal fractions from rabbit kidney medulla. In the plasma membranes and mitochondria, but not in microsomal fractions, Ca2+ ions stimulate the activity of phospholipase A2, yielding selective release of arachidonic acid and linoleic acid and concomitant increase in prostaglandin E2 formation.

scholarly journals Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices

1985 ◽  
Vol 232 (3) ◽  
pp. 625-628 ◽  
Author(s):  
Y Fujimoto ◽  
H Uno ◽  
C Kagen ◽  
T Ueno ◽  
T Fujita
Keyword(s):  
Arachidonic Acid ◽  
Phosphatidic Acid ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Rabbit Kidney ◽  
Dependent Manner ◽  
Kidney Medulla ◽  
Sequential Action ◽  
Acid Release ◽  
Dose Dependent

The effect of diarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. The addition of diarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. At three concentrations (10, 50 and 100 microM), increases in prostaglandin E2 formation induced by exogenous diarachidonin were 2-fold greater than those induced by exogenous arachidonic acid. Diacylglycerol or phosphatidic acid from egg lecithin had little or no effect on prostaglandin E2 production. Moreover, EGTA failed to inhibit diarachidonin-stimulated prostaglandin E2 formation, indicating that the stimulatory effect of diarachidonin is not mediated through the activation of endogenous phospholipase A2 (including phosphatidic acid-specific phospholipase A2). These results are discussed in the light of our former hypothesis that arachidonic acid release from kidney medulla phospholipids might occur through the sequential action of a phospholipase C coupled to diacylglycerol and monoacylglycerol lipases [Fujimoto, Akamatsu, Hattori & Fujita (1984) Biochem. J. 218, 69-74].

scholarly journals Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices

1984 ◽  
Vol 218 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Y Fujimoto ◽  
N Akamatsu ◽  
A Hattori ◽  
T Fujita
Keyword(s):  
Fatty Acids ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Phospholipase C ◽  
Unsaturated Fatty Acids ◽  
Rabbit Kidney ◽  
Dependent Manner ◽  
Kidney Medulla ◽  
Diacylglycerol Lipase ◽  
Dose Dependent

We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 production in a dose-dependent manner. At the maximal effective concentrations (0.5 unit of phospholipase A2/ml, 2 units of phospholipase C/ml), phospholipase C increased prostaglandin E2 formation to the level observed with phospholipase A2. Phospholipase A2 enhanced the release only of unsaturated fatty acids, whereas phospholipase C stimulated the release of individual free fatty acids (C 16:0, C 18:0, C 18:1, C 18:2 and C 20:4). Moreover, p-bromophenacyl bromide inhibited phospholipase A2-stimulated prostaglandin E2 production and the release of fatty acids, but it had no influence on prostaglandin E2 formation and the release of fatty acids increased by phospholipase C, indicating that the stimulatory effect of phospholipase C is not mediated through the activation of endogenous phospholipase A2. These results suggest the presence of diacylglycerol lipase and monoacylglycerol lipase in the kidney and the importance of this pathway in prostaglandin synthesis by the kidney.

scholarly journals The interaction between lipid peroxidation and prostaglandin synthesis in rabbit kidney-medulla slices

1983 ◽  
Vol 212 (1) ◽  
pp. 167-171 ◽  
Author(s):  
Y Fujimoto ◽  
H Tanioka ◽  
I Keshi ◽  
T Fujita
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Inhibitory Effect ◽  
Prostaglandin Synthesis ◽  
Rabbit Kidney ◽  
Kidney Medulla ◽  
Prostaglandin Endoperoxide Synthase ◽  
Generating System

Lipid peroxidation induced by ascorbic acid and Fe2+ was inhibited by mepacrine (phospholipase A2 inhibitor) and aspirin (prostaglandin cyclo-oxygenase inhibitor) in rabbit kidney-medulla slices. Moreover, ascorbic acid and Fe2+ potentiated the inhibitory effect on prostaglandin E2 formation by mepacrine, but they had no influence on prostaglandin E2 production decreased by aspirin. Lipid peroxidation induced by ascorbic acid and Fe2+ appears to be affecting the activity of prostaglandin endoperoxide synthase. These results suggest that lipid peroxidation is connected closely with the prostaglandin-generating system, and it has the potential to modulate the turnover of arachidonic acid and prostaglandin synthesis.

scholarly journals Biosynthesis of platelet-activating factor (PAF) in human polymorphonuclear leucocytes. The role of lyso-PAF disposal and free arachidonic acid

1990 ◽  
Vol 268 (1) ◽  
pp. 91-98 ◽  
Author(s):  
M D C Garcia ◽  
S Fernandez-Gallardo ◽  
M A Gijon ◽  
C Garcia ◽  
M L Nieto ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
Eicosatetraenoic Acid ◽  
Polymorphonuclear Leucocytes ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Dose Dependent

Theophylline and 1-methyl-3-isobutylxanthine (MIX), compounds that block eicosanoid formation and modulate phospholipase A2 activity, inhibited in a dose-dependent manner the formation of both leukotriene B4 (LTB4) and platelet-activating factor (PAF) by human polymorphonuclear leucocytes (PMN) in response to ionophore A23187. Theophylline and MIX lacked any inhibitory effect on acetyl-CoA: lyso-PAF acetyltransferase activity, which is the rate-limiting step for PAF biosynthesis in PMN. The effect of theophylline and MIX on PAF formation could be reversed by incubating the cells in the presence of 1-10 microM exogenous lyso-PAF. Incubation of PMN homogenates in the presence of unsaturated non-esterified fatty acids resulted in dose-dependent inhibition of the acetyltransferase. This effect was linked to the presence of a free carboxyl group, since both arachidonic acid methyl ester and palmitoyl-arachidonoyl phosphatidylcholine lacked inhibitory activity. This inhibitory effect was also dependent on the number of double bonds, since arachidonic acid (C20:4) and eicosapentaenoic acid (C20:5) displayed maximal effect. Kinetic analysis showed that the effect of arachidonic acid was consistent with competitive inhibition, with a Ki value of about 19 microM. Oxidative metabolites of arachidonic acid showed a lesser inhibitory effect with the following order of potency: arachidonic acid greater than 15-HETE (15-hydroxy-6,8,11,14-eicosatetraenoic acid) greater than LTB4 greater than 5-HETE (5-hydroxy-6,8,11,14-eicosatetraenoic acid) greater than lipoxin A4. Examination of enzymes involved in CoA-dependent acylation revealed a low activity of both arachidonoyl-CoA synthetase and arachidonoyl-CoA: lyso-PAF arachidonoyltransferase. These data indicate a strong influence on PAF biosynthesis of the products of the phospholipase A2 reaction, with lyso-PAF disposal being a critical event for PAF formation, and unsaturated fatty acids acting as feed-back inhibitors. The conversion of arachidonic acid via oxidative metabolism into less active inhibitors of acetyl-CoA:lyso-PAF acetyltransferase seems to be an additional mechanism of modulation of this enzyme activity, linked to the function of lipoxygenases. Finally, the enzyme activities involved in arachidonoyl-CoA-dependent acylation of lyso-PAF show a low efficiency in capturing arachidonic acid.

scholarly journals Enzymic coupling of acylhydrolase and prostaglandin synthase activities in subcellular fractions from rabbit renal medulla

1982 ◽  
Vol 201 (3) ◽  
pp. 635-640 ◽  
Author(s):  
Arie Erman ◽  
Ruth Azuri ◽  
Amiram Raz
Keyword(s):  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Prostaglandin E2 ◽  
Subcellular Fractions ◽  
Rabbit Kidney ◽  
Generation Process ◽  
Kidney Medulla ◽  
Prostaglandin Biosynthesis ◽  
Prostaglandin Synthase ◽  
Mitochondrial Fractions

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.

scholarly journals Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices

1984 ◽  
Vol 36 ◽  
pp. 95
Author(s):  
Tadashi Fujita ◽  
Yohko Fujimoto ◽  
Eiko Toibana ◽  
Hidetoshi Tanioka ◽  
Taku Yamamoto
Keyword(s):  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Rabbit Kidney ◽  
Kidney Medulla ◽  
Stimulation Of

scholarly journals Arachidonic acid release from rat Leydig cells: the involvement of G protein, phospholipase A2 and regulation of cAMP production

2002 ◽  
Vol 172 (1) ◽  
pp. 95-104 ◽  
Author(s):  
AM Ronco ◽  
PF Moraga ◽  
MN Llanos
Keyword(s):  
Arachidonic Acid ◽  
Fatty Acid ◽  
G Protein ◽  
G Proteins ◽  
Pertussis Toxin ◽  
Leydig Cells ◽  
Inhibitory Effect ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Camp Production

We have previously demonstrated that the release of arachidonic acid (AA) from human chorionic gonadotropin (hCG)-stimulated Leydig cells occurs in a dose- and time-dependent manner. In addition, the amount of AA released was dependent on the hormone-receptor interaction and the concentration of LH-hCG binding sites on the cell surface. The present study was conducted to evaluate the involvement of phospholipase A(2) (PLA(2)) and G proteins in AA release from hormonally stimulated rat Leydig cells, and the possible role of this fatty acid in cAMP production. Cells were first prelabelled with [(14)C]AA to incorporate the fatty acid into cell phospholipids, and then treated in different ways to evaluate AA release. hCG (25 mIU) increased the release of AA to 180+/-12% when compared with AA released from control cells, arbitrarily set as 100%. Mepacrine and parabromophenacyl bromide (pBpB), two PLA(2) inhibitors, decreased the hormone-stimulated AA release to 85+/-9 and 70+/-24% respectively. Conversely, melittin, a PLA(2) stimulator, increased the release of AA up to 200% over control. The inhibitory effect of mepacrine on the release of AA was evident in hCG-treated Leydig cells, but not in the melittin-treated cells. To determine if the release of AA was also mediated through a G protein, cells were first permeabilized and subsequently treated with pertussis toxin or GTPgammaS, a non-hydrolyzable analog of GTP. Results demonstrate that GTPgammaS was able to induce a similar level of the release of AA as hCG. In addition, pertussis toxin completely abolished the stimulatory effect of hCG on the release of AA, indicating that a member of the G(i) family was involved in the hCG-dependent release of AA. Cells treated with PLA(2) inhibitors did not modify cAMP production, but exogenously added AA significantly reduced cAMP production from hCG-treated Leydig cells, in a manner dependent on the concentration of AA and hCG. Results presented here suggest an involvement of PLA(2) and G proteins in the release of AA from hCG-stimulated Leydig cells, and under particular conditions, regulation of cAMP production by this fatty acid in these cells.

scholarly journals Involvement of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and invasion of human multiple myeloma cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1925 ◽  
Author(s):  
Jing Shao ◽  
Hongxiang Wang ◽  
Guolin Yuan ◽  
Zhichao Chen ◽  
Qiubai Li
Keyword(s):  
Multiple Myeloma ◽  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Biological Effects ◽  
Inhibitory Effect ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
The Matrix ◽  
Human Multiple Myeloma ◽  
Proliferation And Invasion

Cytochrome P450 (CYP) epoxygenases and the metabolites epoxyeicosatrienoic acids (EETs) exert multiple biological effects in various malignancies. We have previously found EETs to be secreted by multiple myeloma (MM) cells and to be involved in MM angiogenesis, but the role of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and mobility of MM cells remains unknown. In the present study, we found that MM cell lines generated detectable levels of 11,12-EET/14,15-EET and that increased levels of EETs were found in the serum of MM patients compared to healthy donors. The addition of exogenous EETs induced significantly enhanced proliferation of MM cells, whereas 17-octadecynoic acid (17-ODYA), an inhibitor of the CYP epoxygenase pathway, inhibited the viability and proliferation of MM cells. Moreover, this inhibitory effect could be successfully reversed by exogenous EETs. 17-ODYA also inhibited the motility of MM cells in a time-dependent manner, with a reduction of the gelatinolytic activity and protein expression of the matrix metalloproteinases (MMP)-2 and MMP-9. These results suggest the CYP epoxygenase pathway to be involved in the proliferation and invasion of MM cells, for which 17-ODYA could be a promising therapeutic drug.

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