I thought I'd create this thread as a kind of archive for new arachidonic acid studies that seem particularly good.
Here are a couple:
Pharmacol Rev. 2006 Sep;58(3):591-620.
Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders.
Farooqui AA, Ong WY, Horrocks LA.
The phospholipase A(2) family includes secretory phospholipase A(2), cytosolic phospholipase A(2), plasmalogen-selective phospholipase A(2), and calcium-independent phospholipase A(2). It is generally thought that the release of arachidonic acid by cytosolic phospholipase A(2) is the rate-limiting step in the generation of eicosanoids and platelet activating factor. These lipid mediators play critical roles in the initiation and modulation of inflammation and oxidative stress. Neurological disorders, such as ischemia, spinal cord injury, Alzheimer's disease, multiple sclerosis, prion diseases, and epilepsy are characterized by inflammatory reactions, oxidative stress, altered phospholipid metabolism, accumulation of lipid peroxides, and increased phospholipase A(2) activity. Increased activities of phospholipases A(2) and generation of lipid mediators may be involved in oxidative stress and neuroinflammation associated with the above neurological disorders. Several phospholipase A(2) inhibitors have been recently discovered and used for the treatment of ischemia and other neurological diseases in cell culture and animal models. At this time very little is known about in vivo neurochemical effects, mechanism of action, or toxicity of phospholipase A(2) inhibitors in human or animal models of neurological disorders. In kainic acid-mediated neurotoxicity, the activities of phospholipase A(2) isoforms and their immunoreactivities are markedly increased and phospholipase A(2) inhibitors, quinacrine and chloroquine, arachidonyl trifluoromethyl ketone, bromoenol lactone, cytidine 5-diphosphoamines, and vitamin E, not only inhibit phospholipase A(2) activity and immunoreactivity but also prevent neurodegeneration, suggesting that phospholipase A(2) is involved in the neurodegenerative process. This also suggests that phospholipase A(2) inhibitors can be used as neuroprotectants and anti-inflammatory agents against neurodegenerative processes in neurodegenerative diseases.
Arterioscler Thromb Vasc Biol. 2006 Sep 14; [Epub ahead of print]
Phospholipase A2-Modified Low-Density Lipoprotein Activates the Phosphatidylinositol 3-Kinase-Akt Pathway and Increases Cell Survival in Monocytic Cells.
Namgaladze D, Brune B.
OBJECTIVE: Monocyte survival is an important determinant in the development of atherosclerotic lesions. We investigated the influence of phospholipase A2-modified LDL (PLA-LDL), a pro-atherogenic factor, on activation of the pro-survival kinase Akt and cell death in monocytic cells. METHODS AND RESULTS: PLA-LDL induced robust phosphorylation and activation of Akt in THP1 cells. It also attenuated oxidative stress-induced cell death, an effect abolished by phosphatidylinositol 3-kinase (PI3K) inhibition. In addition, PLA-LDL increased survival of human monocytes. We noticed that lipid products derived from LDL phospholipolysis are mediators of PLA-LDL-induced Akt activation. Arachidonic acid, which is released on phospholipase treatment of LDL, induced Akt phosphorylation and increased cell survival, whereas lysophosphatidylcholine, another compound generated by LDL phospholipolysis, induced only transient Akt phosphorylation and was cytotoxic. CONCLUSIONS: Our data indicate that PLA-LDL induces activation of the PI3K-Akt pathway and promotes monocytic cell survival, which may contribute to the pro-atherogenic effects of phospholipase A2-modified LDL.
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