scholarly journals On the mechanism by which hormones induce the release of Ca2+ from mitochondria in the liver cell

1982 ◽  
Vol 206 (1) ◽  
pp. 121-129 ◽  
Author(s):  
J A Whiting ◽  
G J Barritt
Keyword(s):  
Arachidonic Acid ◽  
Liver Cell ◽  
Acid Metabolism ◽  
Isolated Hepatocytes ◽  
Liver Mitochondria ◽  
Arachidonic Acid Metabolism ◽  
Ruthenium Red ◽  
Ionophore A23187 ◽  
Phosphate Ions ◽  
Subsequent Addition

1. The abilities of dinitrophenol, NaCl, Ruthenium Red and the Ca2+-selective ionophore A23187 to release 45 Ca2+ from isolated hepatocytes and liver mitochondria (incubated at 37 degrees C in the presence of 0.1 microM-free Ca2+, Mg2+, ATP and phosphate ions) were compared with the action of adrenaline on 45Ca2+ release from isolated hepatocytes. The effects of adrenaline were most closely described by those of the ionophore A23187. 2. In isolated hepatocytes, a release of 45Ca2+ and stimulation of O2 utilization similar to that induced by adrenaline was observed in the presence of 500 and 20 microM-arachidonic acid respectively. The effect of arachidonic acid on 45Ca2+ release was not specific for this unsaturated fatty acid. 3. Inhibitors of arachidonic acid metabolism, including indomethacin and eicosa-5,811,14-tetraynoic acid, did not block the effects of adrenaline on 45Ca2+ or glucose release from isolated hepatocytes. 4. The ability of adrenaline to stimulate 45Ca2+ release from isolated hepatocytes was rapidly reversed after the subsequent addition of phenoxybenzamine to the cell suspension, and was completely blocked by 0.5 mM-dibucaine. 5. The results are consistent with the action of a Ca2+-selective ionophore in the mechanism by which adrenaline induces the release of Ca2+ from mitochondria in the liver cell and indicate that it is unlikely that arachidonic acid or a metabolite of arachidonic acid is involved in this process.

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.

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.

scholarly journals Effects of lysophospholipids on Ca2+ transport in rat liver mitochondria incubated at physiological Ca2+ concentrations in the presence of Mg2+, phosphate and ATP at 37° C

1984 ◽  
Vol 224 (2) ◽  
pp. 423-430 ◽  
Author(s):  
S Dalton ◽  
B P Hughes ◽  
G J Barritt
Keyword(s):  
Plasma Membrane ◽  
Rat Liver ◽  
Isolated Hepatocytes ◽  
Liver Mitochondria ◽  
Ruthenium Red ◽  
Rat Liver Mitochondria ◽  
Intact Cells ◽  
Phosphate Ions ◽  
Low Concentrations ◽  
Significant Impairment

Lysophospholipids caused the release of 45Ca2+ from isolated rat liver mitochondria incubated at 37 degrees C in the presence of low concentrations of free Ca2+, ATP, Mg2+, and phosphate ions. The concentrations of lysophosphatidylethanolamine, lysophosphatidylcholine, lysophosphatidic acid and lysophosphatidylinositol which gave half-maximal effects were 5, 26, 40 and 56 microM, respectively. The effects of lysophosphatidylethanolamine were not associated with a significant impairment of the integrity of the mitochondria as monitored by measurement of membrane potential and the rate of respiration. Lysophosphatidylethanolamine did not induce the release of Ca2+ from a microsomal fraction, or enhance Ca2+ inflow across the plasma membrane of intact cells, but did release Ca2+ from an homogenate prepared from isolated hepatocytes and incubated under the same conditions as isolated mitochondria. The proportion of mitochondrial 45Ca2+ released by lysophosphatidylethanolamine was not markedly affected by altering the total amount of Ca2+ in the mitochondria, the concentration of extramitochondrial Mg2+, by the addition of Ruthenium Red, or when oleoyl lysophosphatidylethanolamine was employed instead of the palmitoyl derivative. The effects of 5 microM-lysophosphatidylethanolamine were reversed by washing the mitochondria. The possibility that lysophosphatidylethanolamine acts to release Ca2+ from mitochondria in intact hepatocytes following the binding of Ca2+-dependent hormones to the plasma membrane is briefly discussed.

scholarly journals Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2

Cell Research ◽  
2010 ◽  
Vol 20 (5) ◽  
pp. 563-575 ◽  
Author(s):  
Changliang Shan ◽  
Fuqing Xu ◽  
Shuai Zhang ◽  
Jiacong You ◽  
Xiaona You ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Arachidonic Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Cell ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
X Protein ◽  
B Virus

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.

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.

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