Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid

1987 ◽  
Vol 32 (6) ◽  
pp. 577-582 ◽  
Author(s):  
O. H. Nielsen ◽  
K. Bukhave ◽  
J. Elmgreen ◽  
I. Ahnfelt-R�nne
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Human Neutrophils ◽  
Aminosalicylic Acid ◽  
Lipoxygenase Pathway

scholarly journals Effects of calmodulin and lipoxygenase inhibitors on LH (lutropin)- and LHRH (luliberin)-agonist-stimulated steroidogenesis in rat Leydig cells

1985 ◽  
Vol 232 (1) ◽  
pp. 55-59 ◽  
Author(s):  
M H Sullivan ◽  
B A Cooke
Keyword(s):  
Arachidonic Acid ◽  
Leydig Cells ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Lhrh Agonist ◽  
Lipoxygenase Pathway ◽  
Lipoxygenase Inhibitors ◽  
Testosterone Production

The results of this study, carried out with purified rat Leydig cells, indicate that there are no major differences in the stimulating effects of lutropin (LH) and luliberin (LHRH) agonists on steroidogenesis via mechanisms that are dependent on Ca2+. This was demonstrated by using inhibitors of calmodulin and the lipoxygenase pathways of arachidonic acid metabolism. All three calmodulin inhibitors used (calmidazolium, trifluoperazine and chlorpromazine) were shown to block LH- and LHRH-agonist-stimulated steroidogenesis. This probably occurred at the step of cholesterol transport to the mitochondria. Similarly, three lipoxygenase inhibitors (nordihydroguaiaretic acid, BW755c and benoxaprofen), inhibited both LH- and LHRH-agonist-stimulated steroidogenesis. The amounts of the inhibitors required were similar for LH- and LHRH-agonist-stimulated steroidogenesis. Steroidogenesis stimulated by the Ca2+ ionophore A23187 was also inhibited, but higher concentrations of the inhibitors were required. Indomethacin (a cyclo-oxygenase inhibitor) increased LHRH-agonist-stimulated steroidogenesis;this is consistent with the role of the products of arachidonic acid metabolism via the alternative, lipoxygenase, pathway. The potentiation of LH-stimulated testosterone production by LHRH agonist was unaffected by indomethacin or by lipoxygenase inhibitors at concentrations that inhibited LH-stimulated testosterone production by 75-100%. It was not possible to eliminate a role of calmodulin in modulating the potentiation, although higher concentrations of the inhibitors were generally required to negate the potentiation than to inhibit LH- or LHRH-agonist-stimulated testosterone production.

Effect of protein kinase C activating agents on respiratory glycoconjugate release from feline airways

1991 ◽  
Vol 261 (6) ◽  
pp. L415-L423 ◽  
Author(s):  
R. D. Rieves ◽  
J. D. Lundgren ◽  
C. Logun ◽  
T. Wu ◽  
J. H. Shelhamer
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Acid Metabolism ◽  
Culture Media ◽  
Experimental Period ◽  
Arachidonic Acid Metabolism ◽  
Lipoxygenase Pathway ◽  
Kinase C ◽  
Dose Dependent

Abnormal regulation of airway glycoprotein secretion may underlie many respiratory diseases. Experimental activation of the protein kinase C (PKC) family of cytosolic enzymes has been shown to induce a secretory response in many tissues. To estimate the effect of PKC activation on airway secretion, alteration in the amount of radiolabeled respiratory glycoconjugate (RGC) released into culture media was determined following feline airway explant exposure to PKC activating agents. Exposure to two known activators of PKC, phorbol 12-myristate 13-acetate (PMA) and mezerein (MEZ), resulted in profound increases in respiratory glycoconjugate release over a seven day experimental period. The response evolved over several hours and was dose dependent. Maximal RGC release, 90% above control, occurred 2 days after exposure to either PMA or MEZ. Pharmacological inhibition of the PKC effect using two PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphingosine, resulted in dose-dependent antagonism of the maximal PMA (10(-7) M)-stimulated RGC release, suggesting altered PKC activity was responsible for augmenting RGC release. Since altered arachidonic acid metabolism has been implicated in mediating some PKC effects, eicosanoids were assayed in airway explant supernatants following PMA exposure. Enhanced release of both cyclooxygenase and lipoxygenase pathway products was detected by radioimmunoassay. Cotreatment of explants with PMA and an inhibitor of oxidative arachidonic acid metabolism, nordihydroguaiaretic acid, blocked RGC release. These data demonstrate prolonged augmentation of respiratory glycoconjugate release from airway explants following exposure to PKC-activating agents.

Evidence for the presence of phospholipid hydroperoxide glutathione peroxidase in human platelets: implications for its involvement in the regulatory network of the 12-lipoxygenase pathway of arachidonic acid metabolism

2000 ◽  
Vol 353 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Mark SUTHERLAND ◽  
Pattabhiraman SHANKARANARAYANAN ◽  
Tankred SCHEWE ◽  
Santosh NIGAM
Keyword(s):  
Arachidonic Acid ◽  
Glutathione Peroxidase ◽  
Regulatory Network ◽  
Acid Metabolism ◽  
Human Platelets ◽  
Arachidonic Acid Metabolism ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Lipoxygenase Pathway ◽  
Phospholipid Hydroperoxide ◽  
12 Lipoxygenase

The 12-lipoxygenase pathway of arachidonic acid metabolism in platelets and other cells is bifurcated into a reduction route yielding 12-hydroxyeicosatetraenoic acid (12-HETE) and an isomerization route forming hepoxilins. Here we show for the first time the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPx) protein and its activity in platelets. The ratio of the activity of PHGPx to that of cytosolic glutathione peroxidase (GPx-1) was consistently found to be approx. 1:60 in platelets and UT7 megakaryoblasts. Moreover, short-lived PHGPx mRNA was detected in megakaryocytes but not in platelets. Carboxymethylation of selenium-containing glutathione peroxidases by iodoacetate, which results in the inactivation of PHGPx and GPx-1 without inhibition of 12-lipoxygenase, markedly altered the pattern of arachidonic acid metabolism in human platelets. Whereas the formation of 12-HETE was inhibited by 80%, a concomitant accumulation of 12-hydroperoxyeicosatetraenoic acid (12-HpETE) by two orders of magnitude as well as the formation of hepoxilins A3 and B3 were observed. The formation of hepoxilins also occurred when 12-HpETE was added to untreated platelets. In selenium-deficient UT7 cells, which were devoid of GPx-1 but not of PHGPx, the reduction of 12-HPETE was retained, albeit with a lower rate than in control cells containing GPx-1. We therefore believe that both GPx-1 and PHGPx are involved in the regulatory network of the 12-lipoxygenase pathway in platelets and other mammalian cells. Moreover, the diminution of hydroperoxide tone in platelets incubated with arachidonic acid leads primarily to the formation of 12-HETE, whereas the increase in hydroperoxide tone (a situation found under oxidative stress or selenium deficiency or on incubation with 12-HPETE) partly diverts the 12-lipoxygenase pathway from the reduction route to the isomerization route, thus resulting in the formation of hepoxilins.

Adrenal synthesis of corticosterone in response to ACTH in rats is influenced by leukotriene A4 and by lipoxygenase intermediates

1987 ◽  
Vol 112 (2) ◽  
pp. 253-258 ◽  
Author(s):  
D. B. Jones ◽  
D. Marante ◽  
B. C. Williams ◽  
C. R. W. Edwards
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Acid Metabolism ◽  
Cell System ◽  
Arachidonic Acid Metabolism ◽  
Lipoxygenase Pathway ◽  
Adrenal Cells ◽  
Corticosterone Secretion ◽  
Leukotriene A4 ◽  
Stimulation Of

ABSTRACT The possible involvement of the lipoxygenase pathway of arachidonic acid metabolism in the events which take place during ACTH-induced stimulation of corticosterone secretion has been studied using an isolated rat adrenal cell system. Incubation with arachidonic acid resulted in an inhibition of ACTH-stimulated corticosterone production. The lipoxygenase pathway inhibitors nordihydroguaretic acid (NDGA), eicosatetraynoic acid (ETYA) and compound BW755C also produced inhibition of ACTH-stimulated corticosterone synthesis. The concentrations of the inhibitors at which 50% inhibition occurred were 15, 34 and 37 μmol/l respectively. The inhibitions produced by NDGA and ETYA were independent of cyclic AMP output. NDGA also inhibited corticosterone production induced by dibutyryl cyclic AMP but had no effect on corticosterone synthesis induced by pregnenolone. Preincubation of adrenal cells with the lipoxygenase products 5, 12 and 15 hydroxyeicosatetraenoic acid (HETE) and with leukotrienes A4, B4, C4, D4 and E4 resulted in significant inhibitions of corticosterone production in response to ACTH with leukotriene A4 (LTA4) and with 15HETE and 5HETE. Conversely, incubation with glutathione (GSH), which is known to reduce intracellular LTA4 levels, produced stimulation (at 5 mmol GSH/1) and inhibition (at 50 mmol GSH/1) of corticosterone output. These studies suggest that the lipoxygenase pathway may be involved in ACTH-stimulated corticosterone synthesis. J. Endocr. (1987) 112, 253–258

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