Reduction of human recombinant type II phospholipase A(2) and prostaglandin F-2 alpha release by microtubule depolymerizing agents

Munns, M. J., King, R. G. and Rice, G. E. (1999) Reduction of human recombinant type II phospholipase A(2) and prostaglandin F-2 alpha release by microtubule depolymerizing agents. Clinical and Experimental Pharmacology and Physiology, 26 3: 230-235. doi:10.1046/j.1440-1681.1999.03020.x


Author Munns, M. J.
King, R. G.
Rice, G. E.
Title Reduction of human recombinant type II phospholipase A(2) and prostaglandin F-2 alpha release by microtubule depolymerizing agents
Journal name Clinical and Experimental Pharmacology and Physiology   Check publisher's open access policy
ISSN 0305-1870
1440-1681
Publication date 1999-03
Sub-type Article (original research)
DOI 10.1046/j.1440-1681.1999.03020.x
Volume 26
Issue 3
Start page 230
End page 235
Total pages 6
Place of publication Richmond, VIC, Australia
Publisher Wiley-Blackwell
Language eng
Formatted abstract
1. The present study examines the effects of the microtubule depolarizing agent colchicine on secretory type II phospholipase A2 (PLA2) function in Chinese hamster ovary (CHO) cells that specifically overexpress human type II PLA2 and the effect of both colchicine and tubulazole on the release of type II PLA2 and prostaglandin (PG) F(2α) from human placental explants.

2. Significant suppression by colchicine (0.01-10 μmol/L) of PLA2 activity (P < 0.00001), immunoreactive type II PLA2 (irPLA2; P < 0.00001) and PGF(2α) release (P < 0.01) was observed in medium from overexpressing CHO cells. These effects were significantly reduced (P < 0.0001) in the presence of 10 μmol/L taxol, an agent that prevents depolymerization of microtubules. The addition of 30 μmol/L arachidonic acid significantly reduced (P < 0.0001) the inhibition of PGF(2α) production in CHO cell lines.

3. The addition of 1 μmol/L colchicine to human placental explants for 24 h significantly reduced irPLA2 (P < 0.00001) and PGF(2α) production (P < 0.00001). Similarly, 1 μmol/L tubulazole significantly blocked irPLA2 (P < 0.001) and PGF(2α) (P < 0.0001).

4. At 10 μmol/L, taxol significantly reduced irPLA2 inhibition by colchicine (n = 8; P < 0.05) and tubulazole (n = 8; P < 0.05). Similarly, taxol significantly reduced the reduction in PGF(2α) production caused by colchicine (P < 0.001) and by tubulazole (P < 0.001).

5. These results suggest that integrity of the microtubule system is required for PLA2 function and the subsequent production of pro-inflammatory mediators.
Keyword Chinese hamster ovary cells
Colchicine
Microtubule
Phospholipase A(2)
Placenta
Prostaglandin F2 alpha
Taxol
Tubulazole
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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