scholarly journals Role of Mitogen-Activated Protein Kinase-Mediated Cytosolic Phospholipase A2Activation in Arachidonic Acid Metabolism in Human Eosinophils

2001 ◽  
Vol 167 (1) ◽  
pp. 461-468 ◽  
Author(s):  
Xiangdong Zhu ◽  
Hiroyuki Sano ◽  
Kwang Pyo Kim ◽  
Akiko Sano ◽  
Evan Boetticher ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Mitogen Activated Protein Kinase ◽  
Cytosolic Phospholipase ◽  
Mitogen Activated Protein

Superoxide Anion and Hydroxyl Radical Release by Collagen-induced Platelet Aggregation - Role of Arachidonic Acid Metabolism

2000 ◽  
Vol 83 (03) ◽  
pp. 485-490 ◽  
Author(s):  
Daniela Caccese ◽  
Domenico Praticò ◽  
Andrea Ghiselli ◽  
Silvia Natoli ◽  
Pasquale Pignatelli ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Salicylic Acid ◽  
Platelet Aggregation ◽  
Hydroxyl Radical ◽  
Superoxide Anion ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Cytosolic Phospholipase ◽  
Generate Superoxide Anion

SummaryPrevious study demonstrated that platelets undergoing anoxia-reoxygenation generate superoxide anion (O2 −) and hydroxyl radical (OH°) which in turn contribute to activate arachidonic acid (AA) metabolism. However it has not been clarified if oxygen free radicals (OFRs) are also generated when platelets are aggregated by common agonists. We used two probes, i.e. lucigenin and salicylic acid (SA), to measure platelet release of O2 − and OH°, respectively. Among the agonists used, such as ADP, thrombin and collagen, the release of O2 − and OH° was observed mainly when platelets were stimulated with collagen. Such release was inhibited in platelets pre-treated by aspirin suggesting that AA metabolism was the main source of O2 − and OH° formation. To further analyze this relationship, O2 and OH° formation was measured if other oxidant species, namely O2 − and OH°, contribute to the during AA-stimulated platelet aggregation (PA); we observed that O − and OH° release were dependent upon AA concentration. Furthermore, we found that the incubation of platelets with AACOCF3, a potent inhibitor of cytosolic phospholipase A2, inhibited collagen-induced platelet O− and OH° release. The incubation of platelets with salicylic acid or ascorbic acid, which blunt OH° and O2 − respectively, inhibited both collagen-induced platelet aggregation and AA-release. This study demonstrated that collagen-induced platelet aggregation is associated with O2 − and OH° formation, which is dependent upon AA release and analyzed if O2 − and OH° are released during aggregation induced by metabolism.

scholarly journals Role of the p38 Mitogen-Activated Protein Kinase/Cytosolic Phospholipase A2 Signaling Pathway in Blood—Brain Barrier Disruption after Focal Cerebral Ischemia and Reperfusion

2008 ◽  
Vol 28 (10) ◽  
pp. 1686-1696 ◽  
Author(s):  
Chikako Nito ◽  
Hiroshi Kamada ◽  
Hidenori Endo ◽  
Kuniyasu Niizuma ◽  
D Jeannie Myer ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cerebral Ischemia ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Cytosolic Phospholipase ◽  
Mitogen Activated Protein

Cytosolic phospholipase A2 (cPLA2) is a key enzyme that mediates arachidonic acid metabolism, which causes cerebral ischemia-induced oxidative injury, blood—brain barrier (BBB) dysfunction, and edema. Recent reports have shown that p38 mitogen—activated protein kinase (MAPK) is related to phosphorylation and activation of cPLA2 and release of arachidonic acid. However, involvement of the p38 MAPK pathway in cPLA2 activation and of reactive oxygen species in expression of p38 MAPK/cPLA2 after ischemia—reperfusion injury in the brain remains unclear. To address these issues, we used a model of transient focal cerebral ischemia (tFCI) in rats. Western blot analysis showed a significant increase in expression of phospho-p38 MAPK and phospho-cPLA2 in rat brain cortex after tFCI. Activity assays showed that both p38 MAPK and cPLA2 activation markedly increased 1 day after reperfusion. Intraventricular administration of SB203580 significantly suppressed activation and phosphorylation of cPLA2 and attenuated BBB extravasation and subsequent edema. Moreover, overexpression of copper/zinc-superoxide dismutase remarkably diminished activation and phosphorylation of both p38 MAPK and cPLA2 after reperfusion. These findings suggest that the p38 MAPK/cPLA2 pathway may promote BBB disruption with secondary vasogenic edema and that superoxide anions can stimulate this pathway after ischemia—reperfusion injury.

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