Antisense oligonucleotide inhibition of type II phospholipase A2 expression, release and activity in vitro

Lappas, M., Munns, M. J., King, R. G. and Rice, G. E. (2001) Antisense oligonucleotide inhibition of type II phospholipase A2 expression, release and activity in vitro. Placenta, 22 5: 418-424. doi:10.1053/plac.2001.0673


Author Lappas, M.
Munns, M. J.
King, R. G.
Rice, G. E.
Title Antisense oligonucleotide inhibition of type II phospholipase A2 expression, release and activity in vitro
Formatted title
Antisense oligonucleotide inhibition of type II phospholipase A2 expression, release and activity in vitro
Journal name Placenta   Check publisher's open access policy
ISSN 0143-4004
1532-3102
Publication date 2001-05
Sub-type Article (original research)
DOI 10.1053/plac.2001.0673
Volume 22
Issue 5
Start page 418
End page 424
Total pages 7
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Phospholipase A2(PLA2) enzymes that regulate the release of arachidonic acid from cell membrane phospholipids represent a crucial rate-limiting step for the prostaglandin biosynthetic pathway. The aim of this study was to determine the mechanism of action and effects of type II PLA2 antisense oligonucleotides on type II PLA2mRNA relative abundance, and the release of PLA2 enzymatic activity and prostaglandin F(PGF) in vitro. A human placental explant system was used to evaluate the effects of the type II PLA2 specific antisense oligonucleotides A (5′-GGGTGGGTATAGAAGGGCTCC-3′, complementary to the base sequence 697-717 of the type II PLA2 gene) and B (5′-TTTTTGATTTGCTAATTGCTT-3′, complementary to the base sequence 821-841 of the type II PLA2 gene). PLA2 activity released from explants was quantified by radiolabelled substrate assay using14C-phosphatidylethanolamine (PE), and PGF content was analyzed by radioimmunoassay. Compared with control, the release of PLA2 activity and PGF was significantly reduced over the 24-h period by treatment with both antisense oligonucleotides (P< 0.05). At this concentration, type II PLA2mRNA abundance was also significantly reduced by both antisense oligonucleotides A and B (P< 0.05). This data demonstrates the efficacy of antisense oligonucleotide inhibition of secretory PLA2(sPLA2) expression and activity, and the contribution of sPLA2 to placental prostaglandin production.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Centre for Clinical Research Publications
 
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