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CYTOSOLIC PHOSPHOLIPASE A2‑α PARTICIPATES IN LIPID BODY FORMATION AND PGE2 RELEASE IN HUMAN NEUTROPHILS STIMULATED WITH AN L‑AMINO ACID OXIDASE FROM CALLOSELASMA RHODOSTOMA VENOM
Formação de corpo lipídico
PGE2
Neutrófilos humanos
l-aminoácido oxidase
Calloselasma rhodostoma
Venenp
Lipid body formation
Human neutrophils
l‑amino acid oxidase
Calloselasma rhodostoma venom
Author
Affilliation
Abstract
Cr-LAAO, an l-amino acid oxidase isolated from Calloselasma rhodosthoma snake venom, has been
demonstrated as a potent stimulus for neutrophil activation and infammatory mediator production.
However, the mechanisms involved in Cr-LAAO induced neutrophil activation has not been well
characterized. Here we investigated the mechanisms involved in Cr-LAAO-induced lipid body (also
known as lipid droplet) biogenesis and eicosanoid formation in human neutrophils. Using microarray
analysis, we show for the frst time that Cr-LAAO plays a role in the up-regulation of the expression of
genes involved in lipid signalling and metabolism. Those include diferent members of phospholipase
A2, mostly cytosolic phospholipase A2-α (cPLA2-α); and enzymes involved in prostaglandin synthesis
including cyclooxygenases 2 (COX-2), and prostaglandin E synthase (PTGES). In addition, genes
involved in lipid droplet formation, including perilipin 2 and 3 (PLIN 2 and 3) and diacylglycerol
acyltransferase 1 (DGAT1), were also upregulated. Furthermore, increased phosphorylation of
cPLA2-α, lipid droplet biogenesis and PGE2 synthesis were observed in human neutrophils stimulated
with Cr-LAAO. Treatment with cPLA2-α inhibitor (CAY10650) or DGAT-1 inhibitor (A922500)
suppressed lipid droplets formation and PGE2 secretion. In conclusion, we demonstrate for the frst
time the efects of Cr-LAAO to regulate neutrophil lipid metabolism and signalling.
Keywords in Portuguese
Fosfolipase citosólica A2-aFormação de corpo lipídico
PGE2
Neutrófilos humanos
l-aminoácido oxidase
Calloselasma rhodostoma
Venenp
Keywords
Cytosolic phospholipase A2‑αLipid body formation
Human neutrophils
l‑amino acid oxidase
Calloselasma rhodostoma venom
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