scholarly journals Effect of inhibitors of arachidonic acid metabolism on efflux of intracellular enzymes from skeletal muscle following experimental damage

1987 ◽  
Vol 241 (2) ◽  
pp. 403-407 ◽  
Author(s):  
M J Jackson ◽  
A J M Wagenmakers ◽  
R H T Edwards
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Membrane Integrity ◽  
Calcium Ionophore ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Intracellular Enzymes

The role of arachidonic acid metabolism in the efflux of intracellular enzymes from damaged skeletal muscle has been examined in vitro using inhibitors of cyclo-oxygenase and lipoxygenase enzymes. Damage to skeletal muscle induced by either calcium ionophore A23187 (25 microM) or dinitrophenol (1 mM) caused an increase in the efflux of prostaglandins E2 and F2 alpha together with a large efflux of intracellular creatine kinase. Use of a cyclo-oxygenase inhibitor completely prevented the efflux of prostaglandins, but had no effect on creatine kinase efflux. However, several agents having the ability to inhibit lipoxygenase enzymes dramatically reduced creatine kinase efflux following damage. These data suggest that a product or products of lipoxygenase enzymes may be mediators of the changes in plasma membrane integrity which permit efflux of intracellular enzymes as a consequence of skeletal muscle damage.

scholarly journals Calcium ionophore synergizes with bacterial lipopolysaccharides in activating macrophage arachidonic acid metabolism.

1988 ◽  
Vol 167 (2) ◽  
pp. 623-631 ◽  
Author(s):  
A A Aderem ◽  
Z A Cohn
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Calcium Ionophore ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Rapid Release ◽  
Lipoxygenase Products ◽  
Order Of Magnitude ◽  
Bacterial Lipopolysaccharides

LPS, a major component of Gram-negative bacterial cell walls, prime macrophages for greatly enhanced arachidonic acid [20:4] metabolism when the cells are subsequently stimulated. The LPS-primed macrophage has been used as a model system in which to study the role of Ca2+ in the regulation of 20:4 metabolism. The Ca2+ ionophore A23187 (0.1 microM) triggered the rapid release of 20:4 metabolites from LPS-primed macrophages but not from cells not previously exposed to LPS. Macrophages required exposure to LPS for at least 40 min before A23187 became effective as a trigger. A23187 (0.1 microM) also synergized with PMA in activating macrophage 20:4 metabolism. The PMA effect could be distinguished from that of LPS since no preincubation with PMA was required. A23187 greatly increased the amount of lipoxygenase products secreted from LPS-primed macrophages, leukotriene C4 synthesis being increased 150-fold. LPS-primed macrophages, partially permeabilized to Ca2+ with A23187, were used to titrate the Ca2+ concentration dependence of the cyclooxygenase and lipoxygenase pathways. Cyclooxygenase metabolites were detected at an order of magnitude lower Ca2+ concentration than were lipoxygenase products. The data suggest that Ca2+ regulates macrophage 20:4 metabolism at two distinct steps: an increase in intracellular Ca2+ regulates the triggering signal and relatively higher Ca2+ concentrations are required for 5-lipoxygenase activity.

Platelet Activation Induced by lnterleukin-6: Evidence for a Mechanism Involving Arachidonic Acid Metabolism

1994 ◽  
Vol 72 (02) ◽  
pp. 302-308 ◽  
Author(s):  
Leslie Oleksowicz ◽  
Zbignelw Mrowlec ◽  
Dina Zuckerman ◽  
Randi Isaacs ◽  
Janice Dutcher ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Actin Binding ◽  
Insoluble Residue ◽  
Ionophore A23187 ◽  
Dependent Inhibition ◽  
Dose Dependent

SummaryThe effect of IL-6 on in vitro platelet function was investigated. Platelet-rich plasma (PRP) incubated with IL-6 showed a dose dependent enhancement of agonist induced maximum aggregation (AIMA) and secretion of thromboxane B2 (TXB2) as measured by RIA, in short term incubations. Dazoxiben (0.2 to 160 (µM) pretreated PRP incubated with IL-6 and aggregated with ionophore A23187, showed a dose dependent inhibition of TXB2 secretion concomitant with a dose dependent abrogation of IL-6’s enhancement of AIMA. A similar abrogation of AIMA was observed when these experiments were repeated using indomethacin. Further, PRP incubated with IL-6 showed a dose dependent increase in TXB2 and BTG secretion as measured by RIA and an increased incorporation of actin binding protein, talin, and myosin into the cytoskeletal core (triton insoluble residue) as shown by SDS-PAGE. The integrin glycoprotein Ilia (GPIIIa) was also observed to be retained into the cytoskeleton by immunoblot. These results suggest that IL-6 activates platelets in vitro and enhances AIMA via a mechanism involving arachidonic acid metabolism.

Activity of dipyrone on intraplatelet arachidonic acid metabolism: An in vitro study

1989 ◽  
Vol 21 (1) ◽  
pp. 43-50 ◽  
Author(s):  
R ABBATE ◽  
S PINTO ◽  
A GORI ◽  
R PANICCIA ◽  
M COPPO ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Acid Metabolism ◽  
In Vitro Study ◽  
Arachidonic Acid Metabolism ◽  
Vitro Study

scholarly journals Endogenous peroxidase in the nuclear envelope and endoplasmic reticulum of human monocytes in vitro: association with arachidonic acid metabolism

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 491-498 ◽  
Author(s):  
W Deimann ◽  
M Seitz ◽  
D Gemsa ◽  
HD Fahimi
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Synthesis ◽  
Arachidonic Acid ◽  
Nuclear Envelope ◽  
Culture Medium ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Substantial Decrease ◽  
Prostaglandin E

Abstract he development of peroxidase (PO) reaction in the nuclear envelope (NE) and endoplasmic reticulum (ER) of monocytes differentiating in vitro and its relationship with arachidonic acid metabolism were studied. The PO, as visualized by the diaminobenzidine (DAB) technique, appeared in the NE and ER of the majority of monocytes within 24 hours of culture, with a substantial decrease thereafter. The influence of three major groups of agents--inhibitors of PO, of prostanoids, and of protein biosynthesis--upon the development of the PO reaction was examined. When aminotriazole, a PO inhibitor, was added to the culture medium, the appearance of PO was suppressed in the monocytes. The cyclooxygenase blocker, indomethacin, however, did not influence the development of PO. Also the blockers of protein synthesis, puromycin, cycloheximide, and actinomycin D, did not affect the appearance of PO. The prostanoids released from the monocytes, ie, prostaglandin E and thromboxane B2, were determined by radioimmunoassay and showed a time sequence of secretion that corresponded to the appearance of PO in the cells: a marked increase within the first 24 hours with a substantial decrease thereafter. The presence of the PO inhibitors aminotriazole and sodium azide in the culture medium produced a suppression of prostanoid release from the monocytes comparable with that of indomethacin. The data suggest that the PO in the NE and ER of differentiating monocytes in vitro (1) is associated with arachidonic acid metabolism, and (2) is not formed by de novo protein synthesis but rather by an activation process.

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