| dc.contributor.author |
Lopez-Vales, R |
en |
| dc.contributor.author |
Ghasemlou, N |
en |
| dc.contributor.author |
Redensek, A |
en |
| dc.contributor.author |
Kerr, BJ |
en |
| dc.contributor.author |
Barbayianni, E |
en |
| dc.contributor.author |
Antonopoulou, G |
en |
| dc.contributor.author |
Baskakis, C |
en |
| dc.contributor.author |
Rathore, KI |
en |
| dc.contributor.author |
Constantinou-Kokotou, V |
en |
| dc.contributor.author |
Stephens, D |
en |
| dc.contributor.author |
Shimizu, T |
en |
| dc.contributor.author |
Dennis, EA |
en |
| dc.contributor.author |
Kokotos, G |
en |
| dc.contributor.author |
David, S |
en |
| dc.date.accessioned |
2014-06-06T06:51:00Z |
|
| dc.date.available |
2014-06-06T06:51:00Z |
|
| dc.date.issued |
2011 |
en |
| dc.identifier.issn |
08926638 |
en |
| dc.identifier.uri |
http://dx.doi.org/10.1096/fj.11-183186 |
en |
| dc.identifier.uri |
http://62.217.125.90/xmlui/handle/123456789/5266 |
|
| dc.subject |
CNS injury |
en |
| dc.subject |
Lipid metabolism |
en |
| dc.subject |
Prostaglandin receptors |
en |
| dc.subject |
Secondary damage |
en |
| dc.subject.other |
arachidonic acid |
en |
| dc.subject.other |
ax 059 |
en |
| dc.subject.other |
ax 115 |
en |
| dc.subject.other |
enzyme inhibitor |
en |
| dc.subject.other |
fatty acid |
en |
| dc.subject.other |
fkgk 11 |
en |
| dc.subject.other |
gk 115 |
en |
| dc.subject.other |
glycerophospholipid |
en |
| dc.subject.other |
icosanoid |
en |
| dc.subject.other |
lysophospholipid |
en |
| dc.subject.other |
phospholipase A2 |
en |
| dc.subject.other |
phospholipase A2 inhibitor |
en |
| dc.subject.other |
prostaglandin E receptor 1 |
en |
| dc.subject.other |
unclassified drug |
en |
| dc.subject.other |
enzyme inhibitor |
en |
| dc.subject.other |
phospholipase A2 |
en |
| dc.subject.other |
phospholipase A2 group II |
en |
| dc.subject.other |
phospholipase A2 group IV |
en |
| dc.subject.other |
phospholipase A2 group VI |
en |
| dc.subject.other |
Pla2g2a protein, mouse |
en |
| dc.subject.other |
Pla2g4a protein, mouse |
en |
| dc.subject.other |
Pla2g6 protein, mouse |
en |
| dc.subject.other |
prostaglandin E receptor 1 |
en |
| dc.subject.other |
animal experiment |
en |
| dc.subject.other |
animal model |
en |
| dc.subject.other |
animal tissue |
en |
| dc.subject.other |
article |
en |
| dc.subject.other |
controlled study |
en |
| dc.subject.other |
cytosol |
en |
| dc.subject.other |
female |
en |
| dc.subject.other |
histopathology |
en |
| dc.subject.other |
inflammation |
en |
| dc.subject.other |
mouse |
en |
| dc.subject.other |
nonhuman |
en |
| dc.subject.other |
priority journal |
en |
| dc.subject.other |
protein expression |
en |
| dc.subject.other |
regulatory mechanism |
en |
| dc.subject.other |
spinal cord injury |
en |
| dc.subject.other |
animal |
en |
| dc.subject.other |
Bagg albino mouse |
en |
| dc.subject.other |
chemistry |
en |
| dc.subject.other |
classification |
en |
| dc.subject.other |
drug antagonism |
en |
| dc.subject.other |
drug effect |
en |
| dc.subject.other |
enzymology |
en |
| dc.subject.other |
genetics |
en |
| dc.subject.other |
locomotion |
en |
| dc.subject.other |
metabolism |
en |
| dc.subject.other |
mouse mutant |
en |
| dc.subject.other |
pathology |
en |
| dc.subject.other |
pathophysiology |
en |
| dc.subject.other |
physiology |
en |
| dc.subject.other |
signal transduction |
en |
| dc.subject.other |
spinal cord injury |
en |
| dc.subject.other |
Animals |
en |
| dc.subject.other |
Enzyme Inhibitors |
en |
| dc.subject.other |
Female |
en |
| dc.subject.other |
Group II Phospholipases A2 |
en |
| dc.subject.other |
Group IV Phospholipases A2 |
en |
| dc.subject.other |
Group VI Phospholipases A2 |
en |
| dc.subject.other |
Locomotion |
en |
| dc.subject.other |
Mice |
en |
| dc.subject.other |
Mice, Inbred BALB C |
en |
| dc.subject.other |
Mice, Knockout |
en |
| dc.subject.other |
Phospholipases A2 |
en |
| dc.subject.other |
Receptor Cross-Talk |
en |
| dc.subject.other |
Receptors, Prostaglandin E, EP1 Subtype |
en |
| dc.subject.other |
Spinal Cord Injuries |
en |
| dc.title |
Phospholipase A2 superfamily members play divergent roles after spinal cord injury |
en |
| heal.type |
journalArticle |
en |
| heal.identifier.primary |
10.1096/fj.11-183186 |
en |
| heal.publicationDate |
2011 |
en |
| heal.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 A 2 (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 (cPLA 2 GIVA) and calcium-independent PLA2 group VIA (iPLA 2 GVIA)], and a secreted form [secreted PLA2group 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. © FASEB. |
en |
| heal.journalName |
FASEB Journal |
en |
| dc.identifier.issue |
12 |
en |
| dc.identifier.volume |
25 |
en |
| dc.identifier.doi |
10.1096/fj.11-183186 |
en |
| dc.identifier.spage |
4240 |
en |
| dc.identifier.epage |
4252 |
en |