Inhibition of Cytosolic Phospholipase A2 in Human Neutrophils by Oxatomide

2001 ◽  
Vol 124 (1-3) ◽  
pp. 367-370
Author(s):  
Massimo Triggiani ◽  
Alfonso Oriente ◽  
Francescopaolo Granata ◽  
Cecilia Calabrese ◽  
Gianni Marone
Keyword(s):  
Phospholipase A ◽  
Human Neutrophils ◽  
Cytosolic Phospholipase

Cytosolic phospholipase A 2 mediates neuronal apoptosis induced by soluble oligomers of the amyloid‐β peptide

2004 ◽  
Vol 19 (1) ◽  
pp. 85-87 ◽  
Author(s):  
Badreddine Kriem ◽  
Isabelle Sponne ◽  
Alexandre Fifre ◽  
Catherine Malaplate‐Armand ◽  
Karine Lozac'h‐Pillot ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Amyloid Β ◽  
Phospholipase A ◽  
Amyloid Β Peptide ◽  
Cytosolic Phospholipase ◽  
Phospholipase A 2

scholarly journals Cytosolic phospholipase A2 and its mode of activation in human neutrophils by opsonized zymosan: Correlation between 42/44 kDa mitogen-activated protein kinase, cytosolic phospholipase A2 and NADPH oxidase

1997 ◽  
Vol 326 (3) ◽  
pp. 867-876 ◽  
Author(s):  
Inbal HAZAN ◽  
Raya DANA ◽  
Yoseph GRANOT ◽  
Rachel LEVY
Keyword(s):  
Protein Kinase ◽  
Nadph Oxidase ◽  
Phospholipase A2 ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Cytosolic Phospholipase A2 ◽  
Human Neutrophils ◽  
Pla2 Activity ◽  
Cytosolic Phospholipase ◽  
Gf 109203X

The role of cytosolic phospholipase A2 (cPLA2) and its mode of activation by opsonized zymosan (OZ) was studied in human neutrophils in comparison with activation by PMA. The activation of cPLA2 by 1 mg/ml OZ or 50 ng/ml PMA is evidenced by its translocation to the membrane fractions on stimulation. This translocation is consistent with dithiothreitol (DTT)-resistant phospholipase A2 (PLA2) activity detected in the membranes of activated cells. Neutrophils stimulated by either OZ or PMA exhibited an immediate stimulation of extracellular-signal-regulated kinases (ERKs). The inhibition of ERKs, DTT-resistant PLA2 and NADPH oxidase activities by the MAP kinase kinase inhibitor PD-98059 indicates that ERKs mediate the activation of cPLA2 and NADPH oxidase stimulated by either OZ or PMA. The protein kinase C (PKC) inhibitor GF-109203X inhibited epidermal growth factor receptor peptide kinase activity, the release of [3H]arachidonic acid, DTT-resistant PLA2 activity and superoxide generation induced by PMA, but did not inhibit any of these activities induced by OZ. PKC activity was similarly inhibited by GF-109203X in membrane fractions separated from neutrophils stimulated by either PMA or OZ. In the presence of the tyrosine kinase inhibitor genistein, ERKs, PLA2 and NADPH oxidase activities were inhibited in cells stimulated by OZ, whereas they were hardly affected in cells stimulated by PMA. The results suggest that the activation of cPLA2 by PMA or OZ is mediated by ERKs. Whereas PMA stimulates ERKs activity through a PKC-dependent pathway, signal transduction stimulated by OZ involves tyrosine kinase activity leading to activation of ERKs via a PKC-independent pathway.

scholarly journals Cytosolic phospholipase A 2 protein as a novel therapeutic target for spinal cord injury

2014 ◽  
Vol 75 (5) ◽  
pp. 644-658 ◽  
Author(s):  
Nai‐Kui Liu ◽  
Ling‐Xiao Deng ◽  
Yi Ping Zhang ◽  
Qing‐Bo Lu ◽  
Xiao‐Fei Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Therapeutic Target ◽  
Phospholipase A ◽  
Cytosolic Phospholipase ◽  
Cord Injury ◽  
Novel Therapeutic ◽  
Phospholipase A 2

scholarly journals Inherited human group IVA cytosolic phospholipase A 2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation

2015 ◽  
Vol 29 (11) ◽  
pp. 4568-4578 ◽  
Author(s):  
Nicholas S. Kirkby ◽  
Daniel M. Reed ◽  
Matthew L. Edin ◽  
Francesca Rauzi ◽  
Stefania Mataragka ◽  
...  
Keyword(s):  
Phospholipase A ◽  
Human Group ◽  
Cytosolic Phospholipase ◽  
Group Iva ◽  
Phospholipase A 2

Synthesis and evaluation of substrate-mimicking cytosolic phospholipase A 2 inhibitors––reducing the lipophilicity of the arachidonyl chain isostere

2004 ◽  
Vol 14 (14) ◽  
pp. 3645-3649 ◽  
Author(s):  
Iain Walters ◽  
Colin Bennion ◽  
Stephen Connolly ◽  
Pamela J Croshaw ◽  
Kim Hardy ◽  
...  
Keyword(s):  
Phospholipase A ◽  
Cytosolic Phospholipase ◽  
Phospholipase A 2

Cytosolic phospholipase A2α regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation

2005 ◽  
Vol 288 (6) ◽  
pp. R1774-R1782 ◽  
Author(s):  
Adam Sapirstein ◽  
Hideyuki Saito ◽  
Sarah J. Texel ◽  
Tarek A. Samad ◽  
Eileen O’Leary ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase 2 ◽  
Phospholipase A ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
The Central Nervous System ◽  
Cox 2 ◽  
The Brain

The products of arachidonic acid metabolism are key mediators of inflammatory responses in the central nervous system, and yet we do not know the mechanisms of their regulation. The phospholipase A2 enzymes are sources of cellular arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE2 in the brain. These studies seek to determine the function of cytosolic phospholipase A2α (cPLA2α) in inflammatory PGE2 production in the brain. We wondered whether cPLA2α functions in inflammation to produce arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these questions in the brains of wild-type mice and mice deficient in cPLA2α (cPLA2α−/−) after systemic administration of LPS. cPLA2α−/− mice had significantly less brain COX-2 mRNA and protein expression in response to LPS than wild-type mice. The reduction in COX-2 was most apparent in the cells of the cerebral blood vessels and the leptomeninges. The brain PGE2 concentration of untreated cPLA2α−/− mice was equal to their wild-type littermates. After LPS treatment, however, the brain concentration of PGE2 was significantly less in cPLA2α−/− than in cPLA2α+/+ mice (24.4 ± 3.8 vs. 49.3 ± 11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude that cPLA2α regulates COX-2 levels and modulates inflammatory PGE2 levels. These results indicate that cPLA2α inhibition is a novel anti-inflammatory strategy that modulates, but does not completely prevent, eicosanoid responses.

Sign in / Sign up

Export Citation Format

Share Document