The FASEB journal, 2011-12, Vol.25 (12), p.4240-4252
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Phospholipase A2 superfamily members play divergent roles after spinal cord injury
- Ist Teil von
- The FASEB journal, 2011-12, Vol.25 (12), p.4240-4252
- Ort / Verlag
- United States: Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2011
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- ABSTRACT Spinal cord injury (SCI) results in permanent loss of motor functions. A significant aspect of the tissue damage and functional loss may be prevenTABLE as it occurs, secondary to the trauma. We show that the phospholipase A2 (PLA2) superfamily plays important roles in SCI. PLA2 enzymes hydrolyze membrane glycerophospholipids to yield a free fatty acid and lysophospholipid. Some free fatty acids (arachidonic acid) give rise to eicosanoids that promote inflammation, while some lysophospholipids (lysophosphatidylcholine) cause demyelination. We show in a mouse model of SCI that two cytosolic forms [calcium‐dependent PLA2 group IVA (cPLA2 GIVA) and calcium‐independent PLA2 group VIA (iPLA2 GVIA)], and a secreted form [secreted PLA2 group IIA (sPLA2 GIIA)] are up‐regulated. Using selective inhibitors and null mice, we show that these PLA2s play differing roles. cPLA2 GIVA mediates protection, whereas sPLA2 GIIA and, to a lesser extent, iPLA2 GVIA are detrimental. Furthermore, completely blocking all three PLA2s worsens outcome, while the most beneficial effects are seen by partial inhibition of all three. The partial inhibitor enhances expression of cPLA2 and mediates its beneficial effects via the prostaglandin EP1 receptor. These findings indicate that drugs that inhibit detrimental forms of PLA2 (sPLA2 and iPLA2) and upregulate the protective form (cPLA2) may be useful for the treatment of SCI.—López‐Vales, R., Ghasemlou, N., Redensek, A., Kerr, B. J., Barbayianni, E., Antonopoulou, G., Baskakis, C., Rathore, K. I., Constantinou‐Kokotou, V., Stephens, D., Shimizu, T., Dennis, E. A., Kokotos, G., David, S. Phospholipase A2 superfamily members play divergent roles after spinal cord injury. FASEB J. 25, 4240–4252 (2011). www.fasebj.org
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.11-183186Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3236632
- Format
- –
- Schlagworte
- Animals, CNS injury, Enzyme Inhibitors - chemistry, Enzyme Inhibitors - therapeutic use, Female, Group II Phospholipases A2 - antagonists & inhibitors, Group II Phospholipases A2 - deficiency, Group II Phospholipases A2 - metabolism, Group IV Phospholipases A2 - antagonists & inhibitors, Group IV Phospholipases A2 - deficiency, Group IV Phospholipases A2 - genetics, Group IV Phospholipases A2 - metabolism, Group VI Phospholipases A2 - antagonists & inhibitors, Group VI Phospholipases A2 - deficiency, Group VI Phospholipases A2 - metabolism, Key Words, lipid metabolism, Locomotion - drug effects, Locomotion - physiology, Mice, Mice, Inbred BALB C, Mice, Knockout, Phospholipase A2 Inhibitors, Phospholipases A2 - classification, Phospholipases A2 - deficiency, Phospholipases A2 - metabolism, prostaglandin receptors, Receptor Cross-Talk, Receptors, Prostaglandin E, EP1 Subtype - metabolism, Research Communications, secondary damage, Spinal Cord Injuries - drug therapy, Spinal Cord Injuries - enzymology, Spinal Cord Injuries - pathology, Spinal Cord Injuries - physiopathology